View source for Monocyte

{{Short description|Subtype of leukocytes}}
{{Infobox cell
| Name        = Monocyte
| Greek       =
| Image       = Blausen 0649 Monocyte (crop).png
| Caption     = 3D rendering of a monocyte
| Image2      = Monocytes, a type of white blood cell (Giemsa stained).jpg
| Caption2    = Monocytes under a [[light microscope]] from a peripheral [[blood smear]] surrounded by [[red blood cell]]s
| Precursor   =
| System      = [[Immune system]]
}}

'''Monocytes''' are a type of leukocyte or [[white blood cell]]. They are the largest type of leukocyte in the blood and can [[cellular differentiation|differentiate]] into [[macrophage]]s and monocyte-derived [[dendritic cell]]s. As a part of the [[vertebrate]] [[innate immune system]] monocytes also influence [[Adaptive immune system|adaptive immune responses]] and exert tissue repair functions.  There are at least three subclasses of monocytes in [[human]] [[blood]] based on their phenotypic receptors.

==Structure==
Monocytes are [[amoeba|amoeboid]] in appearance, and have nongranulated [[cytoplasm]].<ref>{{cite journal |last1=Nichols |first1=Barbara A. |last2=Bainton |first2=Dorothy Ford |last3=Farquhar |first3=Marilyn G. |date=1 August 1971 |title=Differentiation of monocytes |journal=[[Journal of Cell Biology]] |volume=50 |issue=2 |pages=498–515 |doi=10.1083/jcb.50.2.498 |pmc=2108281 |pmid=4107019}}</ref> Thus they are classified as [[agranulocyte]]s, although they might occasionally display some [[azurophil granules]] and/or [[vacuole]]s. With a diameter of 15–22 [[Micrometre|μm]], monocytes are the largest cell type in [[peripheral blood]].<ref name="w192">{{cite journal | last1=Palmer | first1=L. | last2=Briggs | first2=C. | last3=McFadden | first3=S. | last4=Zini | first4=G. | last5=Burthem | first5=J. | last6=Rozenberg | first6=G. | last7=Proytcheva | first7=M. | last8=Machin | first8=S. J. | title=ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features | journal=International Journal of Laboratory Hematology | volume=37 | issue=3 | date=2015 | issn=1751-5521 | doi=10.1111/ijlh.12327 | pages=287–303| pmid=25728865 }}</ref><ref>{{cite journal|url=http://www.histology.leeds.ac.uk/blood/blood_wbc.php|title=The Leeds Histology Guide|first1=Paxton|last1=Steve|first2=Peckham|last2=Michelle|first3=Knibbs|last3=Adele|date=28 April 2018|website=leeds.ac.uk|access-date=28 April 2018|url-status=live|archive-url=https://web.archive.org/web/20171011015456/http://www.histology.leeds.ac.uk/blood/blood_wbc.php|archive-date=11 October 2017}}</ref>  Monocytes are mononuclear cells and the ellipsoidal nucleus is often lobulated/indented, causing a bean-shaped or kidney-shaped appearance.<ref name="m118">{{cite journal | last=Zini | first=Gina | title=How I investigate difficult cells at the optical microscope | journal=International Journal of Laboratory Hematology | volume=43 | issue=3 | date=2021 | issn=1751-5521 | doi=10.1111/ijlh.13437 | pages=346–353| pmid=33342036 }}</ref> Monocytes compose 2% to 10% of all leukocytes in the human body.

==Development==
[[File:Monoblast, promonocyte and monocyte.jpg|thumb|400px|Comparison of monoblast, promonocyte and monocyte.]]
Monocytes are produced by the [[bone marrow]] from precursors called [[monoblast]]s, bipotent cells that differentiated from [[hematopoietic stem cells]].<ref name="Monga">{{cite journal |vauthors=Monga I, Kaur K, Dhanda S |date=March 2022 |title=Revisiting hematopoiesis: applications of the bulk and single-cell transcriptomics dissecting transcriptional heterogeneity in hematopoietic stem cells |journal=[[Briefings in Functional Genomics]] |volume=21 |issue=3 |pages=159–176 |doi=10.1093/bfgp/elac002 |pmid=35265979}}</ref> Monocytes circulate in the bloodstream for about one to three days and then typically migrate into organs throughout the body where they differentiate into [[macrophage]]s and [[dendritic cell]]s.

==Subpopulations==
===In humans===
The first clear description of monocyte subsets by flow cytometry dates back to the late 1980s, when a population of [[CD16]]-positive monocytes was described.<ref>{{cite journal |last1=Ziegler-Heitbrock|first1=H W Loems|last2=Passlick |first2=Bernward |last3=Flieger|first3=Dimitri |title= The Monoclonal Antimonocyte Antibody My4 Stains B Lymphocytes and Two Distinct Monocyte Subsets in Human Peripheral Blood. |journal=Hybridoma |date=December 1988 |volume=7 |issue=6 |pages=521–527 |doi= 10.1089/hyb.1988.7.521|pmid= 2466760 }}</ref><ref>{{cite journal |last1=Passlick|first1=Bernward |last2=Flieger|first2=Dimitri |last3= Ziegler-Heitbrock |first3=H W Loems |title= Characterization of a human monocyte subpopulation coexpressing CD14 and CD16 antigens. |journal=Blood |date=November 1989 |volume=74 |issue=7 |pages=2527–2534 |doi= 10.1182/blood.V74.7.2527.2527 |pmid= 2478233 |doi-access=free }}</ref> Today, three types of monocytes are recognized in human blood:<ref>{{cite journal |last1=Ziegler-Heitbrock |first1=Loems |last2=Ancuta |first2=Petronela |last3=Crowe |first3=Suzanne |last4=Dalod |first4=Marc |last5=Grau |first5=Veronika |last6=Hart |first6=Derek N. |last7=Leenen |first7=Pieter J. M. |last8=Liu |first8=Yong-Jun |last9=MacPherson |first9=Gordon |last10=Randolph |first10=Gwendalyn J. |last11=Scherberich |first11=Juergen |last12=Schmitz |first12=Juergen |last13=Shortman |first13=Ken |last14=Sozzani |first14=Silvano |last15=Strobl |first15=Herbert |last16=Zembala |first16=Marek |last17=Austyn |first17=Jonathan M. |last18=Lutz |first18=Manfred B. |title=Nomenclature of monocytes and dendritic cells in blood |journal=Blood |date=21 October 2010 |volume=116 |issue=16 |pages=e74–e80 |doi=10.1182/blood-2010-02-258558 |pmid=20628149 |hdl=11379/41075 |s2cid=1570404 |hdl-access=free }}</ref>
# The classical monocyte is characterized by high level expression of the [[CD14]] cell surface receptor (CD14<sup>++</sup> CD16<sup>−</sup> monocyte)
# The non-classical monocyte shows low level expression of [[CD14]] and additional co-expression of the [[CD16]] receptor (CD14<sup>+</sup>CD16<sup>++</sup> monocyte).<ref>{{cite journal |last1=Ziegler-Heitbrock |first1=Loems |date=March 2007 |title=The CD14+ CD16+ blood monocytes: their role in infection and inflammation |journal=[[Journal of Leukocyte Biology]] |volume=81 |issue=3 |pages=584–592 |doi=10.1189/jlb.0806510 |pmid=17135573 |doi-access=free |s2cid=31534841}}</ref>
# The intermediate monocyte expresses high levels of [[CD14]] and low levels of [[CD16]] (CD14<sup>++</sup>CD16<sup>+</sup> monocytes).

While in humans the level of CD14 expression can be used to differentiate non-classical and intermediate monocytes, the slan (6-Sulfo LacNAc) cell surface marker was shown to give an unequivocal separation of the two cell types.<ref name="ReferenceA">{{cite journal |last1=Hofer |first1=Thomas P. |last2=Zawada |first2=Adam M. |last3=Frankenberger |first3=Marion |last4=Skokann |first4=Kerstin |last5=Satzl |first5=Anna A. |last6=Gesierich |first6=Wolfgang |last7=Schuberth |first7=Madeleine |last8=Levin |first8=Johannes |last9=Danek |first9=Adrian |last10=Rotter |first10=Björn |last11=Heine |first11=Gunnar H. |last12=Ziegler-Heitbrock |first12=Loems |title=slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation |journal=Blood |date=10 December 2015 |volume=126 |issue=24 |pages=2601–2610 |doi=10.1182/blood-2015-06-651331 |pmid=26443621 |doi-access=free }}</ref><ref>{{cite journal |last1=Hofer |first1=Thomas P. |last2=van de Loosdrecht |first2=Arjan A. |last3=Stahl-Hennig |first3=Christiane |last4=Cassatella |first4=Marco A. |last5=Ziegler-Heitbrock |first5=Loems |date=13 September 2019 |title=6-Sulfo LacNAc (Slan) as a Marker for Non-classical Monocytes |journal=[[Frontiers in Immunology]] |volume=10 |page=2052 |doi=10.3389/fimmu.2019.02052 |pmc=6753898 |pmid=31572354 |doi-access=free}}</ref>

Ghattas et al. state that the "intermediate" monocyte population is likely to be a unique subpopulation of monocytes, as opposed to a developmental step, due to their comparatively high expression of surface receptors involved in reparative processes (including [[vascular endothelial growth factor]] receptors type 1 and 2, [[CXCR4]], and [[Tie-2]]) as well as evidence that the "intermediate" subset is specifically enriched in the bone marrow.<ref>{{cite journal |last1=Ghattas |first1=Angie |last2=Griffiths |first2=Helen R. |last3=Devitt |first3=Andrew |last4=Lip |first4=Gregory Y.H. |last5=Shantsila |first5=Eduard |date=October 2013 |title=Monocytes in Coronary Artery Disease and Atherosclerosis |journal=[[Journal of the American College of Cardiology]] |volume=62 |issue=17 |pages=1541–1551 |doi=10.1016/j.jacc.2013.07.043 |pmid=23973684 |doi-access=free}}</ref>

===In mice===
In mice, monocytes can be divided in two subpopulations. Inflammatory monocytes ([[CX3CR1]]<sup>low</sup>, [[CCR2]]<sup>pos</sup>, [[Ly6C]]<sup>high</sup>, [[PD-L1]]<sup>neg</sup>), which are equivalent to human classical CD14<sup>++</sup> CD16<sup>−</sup> monocytes and resident monocytes ([[CX3CR1]]<sup>high</sup>, [[CCR2]]<sup>neg</sup>, [[Ly6C]]<sup>low</sup>, [[PD-L1]]<sup>pos</sup>), which are equivalent to human non-classical CD14<sup>+</sup> CD16<sup>+</sup> monocytes. Resident monocytes have the ability to patrol along the endothelium wall in the steady state and under inflammatory conditions.<ref>{{cite journal |last1=Carlin |first1=Leo M. |last2=Stamatiades |first2=Efstathios G. |last3=Auffray |first3=Cedric |last4=Hanna |first4=Richard N. |last5=Glover |first5=Leanne |last6=Vizcay-Barrena |first6=Gema |last7=Hedrick |first7=Catherine C. |last8=Cook |first8=H. Terence |last9=Diebold |first9=Sandra |last10=Geissmann |first10=Frederic |title=Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal |journal=Cell |date=April 2013 |volume=153 |issue=2 |pages=362–375 |doi=10.1016/j.cell.2013.03.010 |pmid=23582326 |pmc=3898614 }}</ref><ref>{{cite journal |last1=Auffray |first1=Cedric |last2=Fogg |first2=Darin |last3=Garfa |first3=Meriem |last4=Elain |first4=Gaelle |last5=Join-Lambert |first5=Olivier |last6=Kayal |first6=Samer |last7=Sarnacki |first7=Sabine |last8=Cumano |first8=Ana |last9=Lauvau |first9=Gregoire |last10=Geissmann |first10=Frederic |title=Monitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior |journal=Science |date=3 August 2007 |volume=317 |issue=5838 |pages=666–670 |doi=10.1126/science.1142883 |pmid=17673663 |bibcode=2007Sci...317..666A |s2cid=46067303 }}</ref><ref>{{cite journal |last1=Imhof |first1=Beat A. |last2=Jemelin |first2=Stephane |last3=Ballet |first3=Romain |last4=Vesin |first4=Christian |last5=Schapira |first5=Marc |last6=Karaca |first6=Melis |last7=Emre |first7=Yalin |date=16 August 2016 |title=CCN1/CYR61-mediated meticulous patrolling by Ly6C low monocytes fuels vascular inflammation |journal=[[Proceedings of the National Academy of Sciences]] |volume=113 |issue=33 |pages=E4847–E4856 |doi=10.1073/pnas.1607710113 |pmc=4995973 |pmid=27482114 |bibcode=2016PNAS..113E4847I |doi-access=free}}</ref><ref>{{cite journal |last1=Bianchini |first1=Mariaelvy |last2=Duchêne |first2=Johan |last3=Santovito |first3=Donato |last4=Schloss |first4=Maximilian J. |last5=Evrard |first5=Maximilien |last6=Winkels |first6=Holger |last7=Aslani |first7=Maria |last8=Mohanta |first8=Sarajo K. |last9=Horckmans |first9=Michael |last10=Blanchet |first10=Xavier |last11=Lacy |first11=Michael |date=21 June 2019 |title=PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function |journal=[[Science Immunology]] |volume=4 |issue=36 |article-number=eaar3054 |doi=10.1126/sciimmunol.aar3054 |pmid=31227596 |doi-access=free |last12=von Hundelshausen |first12=Philipp |last13=Atzler |first13=Dorothee |last14=Habenicht |first14=Andreas |last15=Gerdes |first15=Norbert |last16=Pelisek |first16=Jaroslav |last17=Ng |first17=Lai Guan |last18=Steffens |first18=Sabine |last19=Weber |first19=Christian |last20=Megens |first20=Remco T. A. |s2cid=195259881}}</ref>

==Function==
Monocytes are mechanically active cells<ref>{{Cite journal |last1=Evers |first1=Tom M.J. |last2=Sheikhhassani |first2=Vahid |last3=Haks |first3=Mariëlle C. |last4=Storm |first4=Cornelis |last5=Ottenhoff |first5=Tom H.M. |last6=Mashaghi |first6=Alireza |year=2022 |title=Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics |journal=[[iScience]] |volume=25 |issue=1 |article-number=103555 |bibcode=2022iSci...25j3555E |doi=10.1016/j.isci.2021.103555 |pmc=8693412 |pmid=34988399}}</ref> and migrate from blood to an inflammatory site to perform their functions. As explained before, they can differentiate into macrophages and dendritic cells, but the different monocyte subpopulations can also exert specific functions on their own. In general, monocytes and their macrophage and dendritic cell progeny serve three main functions in the immune system. These are [[phagocytosis]], antigen presentation, and [[cytokine]] production.  [[Phagocytosis]] is the process of uptake of microbes and particles followed by digestion and destruction of this material.  Monocytes can perform phagocytosis using intermediary ([[opsonization|opsonising]]) proteins such as [[antibody|antibodies]] or [[complement system|complement]] that coat the pathogen, as well as by binding to the microbe directly via [[pattern recognition receptor]]s that recognize pathogens. Monocytes are also capable of killing infected host cells via [[antibody-dependent cell-mediated cytotoxicity]]. [[Vacuolization]] may be present in a cell that has recently phagocytized foreign matter.

===Differentiation into other effector cells===
Monocytes can migrate into tissues and replenish resident [[macrophage]] populations. Macrophages have a high antimicrobial and phagocytic activity and thereby protect tissues from foreign substances. They are cells that possess a large smooth nucleus, a large area of cytoplasm, and many internal [[Vesicle (biology)|vesicles]] for processing foreign material. Although they can be derived from monocytes, a large proportion is already formed prenatally in the [[yolk sac]] and foetal liver.<ref name="y275">{{cite book | last1=Murphy | first1=Kenneth | last2=Weaver | first2=Casey | title=Janeway Immunologie | chapter=Grundbegriffe der Immunologie | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | date=2018 | pages=3–46 | isbn=978-3-662-56003-7 | pmc=7844863 | doi=10.1007/978-3-662-56004-4_1 | language=de }}</ref>

''In vitro'', monocytes can differentiate into [[dendritic cells]] by adding the cytokines [[granulocyte macrophage colony-stimulating factor]] (GM-CSF) and [[interleukin 4]].<ref name="sallusto">{{cite journal |last1=Sallusto |first1=F |last2=Cella |first2=M |last3=Danieli |first3=C |last4=Lanzavecchia |first4=A |date=1 August 1995 |title=Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. |journal=[[Journal of Experimental Medicine]] |volume=182 |issue=2 |pages=389–400 |doi=10.1084/jem.182.2.389 |pmc=2192110 |pmid=7629501}}</ref> Such monocyte-derived cells do, however, retain the signature of monocytes in their [[transcriptome]] and they cluster with monocytes and not with bona fide dendritic cells.<ref>{{cite journal |last1=Robbins |first1=Scott H |last2=Walzer |first2=Thierry |last3=Dembélé |first3=Doulaye |last4=Thibault |first4=Christelle |last5=Defays |first5=Axel |last6=Bessou |first6=Gilles |last7=Xu |first7=Huichun |last8=Vivier |first8=Eric |last9=Sellars |first9=MacLean |last10=Pierre |first10=Philippe |last11=Sharp |first11=Franck R |date=2008 |title=Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling |journal=[[Genome Biology]] |volume=9 |issue=1 |pages=R17 |doi=10.1186/gb-2008-9-1-r17 |pmc=2395256 |pmid=18218067 |last12=Chan |first12=Susan |last13=Kastner |first13=Philippe |last14=Dalod |first14=Marc |doi-access=free }}</ref>

===Specific functions of monocyte subpopulations===
[[File:Monocyte.svg|thumb|Artist's impression of monocyte]]
Aside from their differentiation capacity, monocytes can also directly regulate immune responses. As explained before, they are able to perform phagocytosis. Cells of the classical subpopulation are the most efficient phagocytes and can additionally secrete inflammation-stimulating factors. The intermediate subpopulation is important for [[antigen presentation]] and [[T lymphocyte]] stimulation.<ref name="d595">{{cite journal | last1=Wong | first1=Kok Loon | last2=Tai | first2=June Jing-Yi | last3=Wong | first3=Wing-Cheong | last4=Han | first4=Hao | last5=Sem | first5=Xiaohui | last6=Yeap | first6=Wei-Hseun | last7=Kourilsky | first7=Philippe | last8=Wong | first8=Siew-Cheng | title=Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets | journal=Blood | volume=118 | issue=5 | date=2011-08-04 | issn=0006-4971 | doi=10.1182/blood-2010-12-326355 | pages=e16–e31| pmid=21653326 }}</ref> Briefly, antigen presentation describes a process during which microbial fragments that are present in the monocytes after phagocytosis are incorporated into MHC molecules. They are then trafficked to the cell surface of the monocytes (or macrophages or dendritic cells) and presented as antigens to activate T lymphocytes, which then mount a specific immune response against the antigen. Non-classical monocytes produce high amounts of pro-inflammatory [[cytokine]]s like [[tumor necrosis factor]] and [[interleukin-12]] after stimulation with microbial products. Furthermore, a monocyte patrolling behavior has been demonstrated in humans both for the classical and the non-classical monocytes, meaning that they slowly move along the [[endothelium]] to examine it for pathogens.<ref>{{cite journal |last1=Collison |first1=Joanna L. |last2=Carlin |first2=Leo M. |last3=Eichmann |first3=Martin |last4=Geissmann |first4=Frederic |last5=Peakman |first5=Mark |date=1 August 2015 |title=Heterogeneity in the Locomotory Behavior of Human Monocyte Subsets over Human Vascular Endothelium In Vitro |journal=[[The Journal of Immunology]] |volume=195 |issue=3 |pages=1162–1170 |doi=10.4049/jimmunol.1401806 |pmid=26085686 |doi-access=free}}</ref> Said et al. showed that activated monocytes express high levels of [[PD 1|PD-1]] which might explain the higher expression of PD-1 in CD14<sup>+</sup>CD16<sup>++</sup> monocytes as compared to CD14<sup>++</sup>CD16<sup>−</sup> monocytes. Triggering monocytes-expressed PD-1 by its [[ligand]] PD-L1 induces IL-10 production, which activates [[CD4]] [[Th2 cells]] and inhibits [[CD4]] [[Th1 cell]] function.<ref>{{cite journal |last1=Said |first1=Elias A |last2=Dupuy |first2=Franck P |last3=Trautmann |first3=Lydie |last4=Zhang |first4=Yuwei |last5=Shi |first5=Yu |last6=El-Far |first6=Mohamed |last7=Hill |first7=Brenna J |last8=Noto |first8=Alessandra |last9=Ancuta |first9=Petronela |last10=Peretz |first10=Yoav |last11=Fonseca |first11=Simone G |date=April 2010 |title=Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection |journal=[[Nature Medicine]] |volume=16 |issue=4 |pages=452–459 |doi=10.1038/nm.2106 |pmc=4229134 |pmid=20208540 |last12=Van Grevenynghe |first12=Julien |last13=Boulassel |first13=Mohamed R |last14=Bruneau |first14=Julie |last15=Shoukry |first15=Naglaa H |last16=Routy |first16=Jean-Pierre |last17=Douek |first17=Daniel C |last18=Haddad |first18=Elias K |last19=Sekaly |first19=Rafick-Pierre}}</ref>
Many factors produced by other cells can regulate the [[chemotaxis]] and other functions of monocytes.  These factors include most particularly [[chemokines]] such as [[monocyte chemotactic protein-1]] (CCL2) and [[CCL7|monocyte chemotactic protein-3 (CCL7)]]; certain [[arachidonic acid]] metabolites such as [[leukotriene B4]] and members of the [[5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid|5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid]] family of OXE1 receptor agonists (e.g., [[5-HETE]] and 5-oxo-ETE); and [[N-Formylmethionine leucyl-phenylalanine]] and other N-formylated [[oligopeptide]]s which are made by bacteria and activate the [[formyl peptide receptor 1]].<ref>{{cite journal |last1=Sozzani |first1=S. |last2=Zhou |first2=D. |last3=Locati |first3=M. |last4=Bernasconi |first4=S. |last5=Luini |first5=W. |last6=Mantovani |first6=A. |last7=O'Flaherty |first7=J. T. |title=Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3. |journal=The Journal of Immunology |date=15 November 1996 |volume=157 |issue=10 |pages=4664–4671 |doi=10.4049/jimmunol.157.10.4664 |pmid=8906847 |s2cid=23499393 |url=https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8906847 |doi-access=free }}</ref>
Other microbial products can directly activate monocytes and this leads to production of pro-inflammatory and, with some delay, of anti-inflammatory [[cytokine]]s. Typical cytokines produced by monocytes are [[tumor necrosis factor|TNF]], [[interleukin-1|IL-1]], and [[interleukin-12|IL-12]].

==Clinical significance==
[[Image:SEM blood cells.jpg|thumb|right|230px|A [[scanning electron microscope]] (SEM) image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.]]
A ''monocyte count'' is part of a [[complete blood count]] and is expressed either as a percentage of monocytes among all white blood cells or as absolute numbers.  Both may be useful, but these cells became valid diagnostic tools only when monocyte subsets are determined.
Monocytic cells may contribute to the severity and disease progression in COVID-19 patients.<ref>{{cite journal |last1=Gómez-Rial |first1=Jose |last2=Rivero-Calle |first2=Irene |last3=Salas |first3=Antonio |last4=Martinón-Torres |first4=Federico |date=22 July 2020 |title=Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy |journal=[[Infection and Drug Resistance]] |volume=13 |pages=2485–2493 |doi=10.2147/IDR.S258639 |pmc=7383015 |pmid=32801787 |doi-access=free }}</ref>

===Monocytosis===
[[Monocytosis]] is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.
Examples of processes that can increase a monocyte count include:
* [[chronic inflammation]]
* [[diabetes]]<ref>{{cite journal |last1=Hoyer |first1=FF |last2=Zhang |first2=X |last3=Coppin |first3=E |last4=Vasamsetti |first4=SB |last5=Modugu |first5=G |last6=Schloss |first6=MJ |last7=Rohde |first7=D |last8=McAlpine |first8=CS |last9=Iwamoto |first9=Y |last10=Libby |first10=P |last11=Naxerova |first11=K |last12=Swirski |first12=F |last13=Dutta |first13=P |last14=Nahrendorf |first14=P |title=Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes |journal=Circulation |date=April 2020 |volume=142 |issue=3 |pages=244–258 |doi=10.1161/CIRCULATIONAHA.120.046038 |pmid=32316750|pmc=7375017 }}</ref>
* [[Stress (medicine)|stress]] response<ref>{{cite journal |last1=Heidt |first1=Timo |last2=Sager |first2=Hendrik B |last3=Courties |first3=Gabriel |last4=Dutta |first4=Partha |last5=Iwamoto |first5=Yoshiko |last6=Zaltsman |first6=Alex |last7=von zur Muhlen |first7=Constantin |last8=Bode |first8=Christoph |last9=Fricchione |first9=Gregory L |last10=Denninger |first10=John |last11=Lin |first11=Charles P |last12=Vinegoni |first12=Claudio |last13=Libby |first13=Peter |last14=Swirski |first14=Filip K |last15=Weissleder |first15=Ralph |last16=Nahrendorf |first16=Matthias |title=Chronic variable stress activates hematopoietic stem cells |journal=Nature Medicine |date=July 2014 |volume=20 |issue=7 |pages=754–758 |doi=10.1038/nm.3589 |pmid=24952646 |pmc=4087061 }}</ref>
* [[Cushing's syndrome]] (hyperadrenocorticism)
* [[immune-mediated disease]]
* [[granuloma]]tous disease
* [[atherosclerosis]]<ref>{{cite journal |last1=Swirski |first1=Filip K. |last2=Libby |first2=Peter |last3=Aikawa |first3=Elena |last4=Alcaide |first4=Pilar |last5=Luscinskas |first5=F. William |last6=Weissleder |first6=Ralph |last7=Pittet |first7=Mikael J. |date=2 January 2007 |title=Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata |journal=[[Journal of Clinical Investigation]] |volume=117 |issue=1 |pages=195–205 |doi=10.1172/JCI29950 |pmc=1716211 |pmid=17200719}}</ref>
* [[necrosis]]
* [[red blood cell]] regeneration
* [[viral fever]]
* [[sarcoidosis]]
* [[chronic myelomonocytic leukemia]] (CMML)
* Resolution of [[fasting]]<ref name="i205">{{cite journal | last1=O'Brien | first1=Conan J.O. | last2=Domingos | first2=Ana I. | title=Old and "hangry" monocytes turn from friend to foe under assault | journal=Immunity | volume=56 | issue=4 | date=2023 | doi=10.1016/j.immuni.2023.03.013 | pages=747–749| pmid=37044065 }}</ref>

A high count of CD14<sup>+</sup>CD16<sup>++</sup> monocytes is found in severe infection ([[sepsis]]).<ref>{{cite journal |last1=Fingerle |first1=G |last2=Pforte |first2=A |last3=Passlick |first3=B |last4=Blumenstein |first4=M |last5=Strobel |first5=M |last6=Ziegler- Heitbrock |first6=Hw |title=The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients |journal=Blood |date=15 November 1993 |volume=82 |issue=10 |pages=3170–3176 |doi=10.1182/blood.v82.10.3170.3170 |pmid=7693040 |doi-access=free }}</ref>

In the field of atherosclerosis, high numbers of the CD14<sup>++</sup>CD16<sup>+</sup> intermediate monocytes were shown to be predictive of cardiovascular events in populations at risk.<ref>{{cite journal |last1=Heine |first1=G.H. |last2=Ulrich |first2=C. |last3=Seibert |first3=E. |last4=Seiler |first4=S. |last5=Marell |first5=J. |last6=Reichart |first6=B. |last7=Krause |first7=M. |last8=Schlitt |first8=A. |last9=Köhler |first9=H. |last10=Girndt |first10=M. |date=March 2008 |title=CD14++CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients |journal=[[Kidney International]] |volume=73 |issue=5 |pages=622–629 |doi=10.1038/sj.ki.5002744 |pmid=18160960 |doi-access=free}}</ref><ref>{{cite journal |last1=Rogacev |first1=Kyrill S. |last2=Cremers |first2=Bodo |last3=Zawada |first3=Adam M. |last4=Seiler |first4=Sarah |last5=Binder |first5=Nadine |last6=Ege |first6=Philipp |last7=Große-Dunker |first7=Gunnar |last8=Heisel |first8=Isabel |last9=Hornof |first9=Florian |last10=Jeken |first10=Jana |last11=Rebling |first11=Niko M. |date=October 2012 |title=CD14++CD16+ Monocytes Independently Predict Cardiovascular Events |journal=[[Journal of the American College of Cardiology]] |volume=60 |issue=16 |pages=1512–1520 |doi=10.1016/j.jacc.2012.07.019 |pmid=22999728 |doi-access=free |last12=Ulrich |first12=Christof |last13=Scheller |first13=Bruno |last14=Böhm |first14=Michael |last15=Fliser |first15=Danilo |last16=Heine |first16=Gunnar H.}}</ref>

CMML is characterized by a persistent monocyte count of > 1000/microL of blood. Analysis of monocyte subsets has demonstrated predominance of classical monocytes and absence of CD14lowCD16+ monocytes.<ref>{{cite journal |last1=Vuckovic |first1=S. |last2=Fearnley |first2=D. B. |last3=Gunningham |first3=S. |last4=Spearing |first4=R. L. |last5=Patton |first5=W. N. |last6=Hart |first6=D. N. J. |date=June 1999 |title=Dendritic cells in chronic myelomonocytic leukaemia: Dendritic Cells in CMML |journal=[[British Journal of Haematology]] |volume=105 |issue=4 |pages=974–985 |doi=10.1046/j.1365-2141.1999.01431.x |pmid=10554809 |doi-access=free |s2cid=22571555}}</ref><ref>{{cite journal |last1=Selimoglu-Buet |first1=Dorothée |last2=Wagner-Ballon |first2=Orianne |last3=Saada |first3=Véronique |last4=Bardet |first4=Valérie |last5=Itzykson |first5=Raphaël |last6=Bencheikh |first6=Laura |last7=Morabito |first7=Margot |last8=Met |first8=Elisabeth |last9=Debord |first9=Camille |last10=Benayoun |first10=Emmanuel |last11=Nloga |first11=Anne-Marie |last12=Fenaux |first12=Pierre |last13=Braun |first13=Thorsten |last14=Willekens |first14=Christophe |last15=Quesnel |first15=Bruno |last16=Adès |first16=Lionel |last17=Fontenay |first17=Michaela |last18=Rameau |first18=Philippe |last19=Droin |first19=Nathalie |last20=Koscielny |first20=Serge |last21=Solary |first21=Eric |title=Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia |journal=Blood |date=4 June 2015 |volume=125 |issue=23 |pages=3618–3626 |doi=10.1182/blood-2015-01-620781 |pmid=25852055 |pmc=4497970 }}</ref> The absence of non-classical monocytes can assist in diagnosis of the disease and the use of slan as a marker can improve specificity.<ref>{{cite journal |last1=Tarfi |first1=Sihem |last2=Badaoui |first2=Bouchra |last3=Freynet |first3=Nicolas |last4=Morabito |first4=Margot |last5=Lafosse |first5=Jeffie |last6=Toma |first6=Andréa |last7=Etienne |first7=Gabriel |last8=Micol |first8=Jean-Baptiste |last9=Sloma |first9=Ivan |last10=Fenaux |first10=Pierre |last11=Solary |first11=Eric |date=April 2020 |title=Disappearance of slan-positive non-classical monocytes for diagnosis of chronic myelomonocytic leukemia with an associated inflammatory state |journal=[[Haematologica]] |volume=105 |issue=4 |pages=e147–e152 |doi=10.3324/haematol.2019.219782 |pmid=31413091 |doi-access=free |last12=Selimoglu-Buet |first12=Dorothée |last13=Wagner-Ballon |first13=Orianne |s2cid=199663779}}</ref>

===Monocytopenia===
[[Monocytopenia]] is a form of [[leukopenia]] associated with a deficiency of monocytes.
A very low count of these cells is found after therapy with immuno-suppressive [[glucocorticoid]]s.<ref>{{cite journal |last1=Fingerle-Rowson |first1=G |last2=Angstwurm |first2=M |last3=Andreesen |first3=R |last4=Ziegler-Heitbrock |first4=HW |date=June 1998 |title=Selective depletion of CD14 + CD16 + monocytes by glucocorticoid therapy: Depletion of CD14+ CD16+ monocytes by glucocorticoids |journal=[[Clinical & Experimental Immunology]] |volume=112 |issue=3 |pages=501–506 |doi=10.1046/j.1365-2249.1998.00617.x |pmc=1904988 |pmid=9649222}}</ref>

Also, non-classical slan+ monocytes are strongly reduced in patients with [[hereditary diffuse leukoencephalopathy with spheroids]], a neurologic disease associated with mutations in the macrophage colony-stimulating factor receptor gene.<ref name="ReferenceA"/>

===Blood content===
[[Image:Reference ranges for blood tests - white blood cells.png|thumb|500px|center|[[Reference ranges for blood tests]] of white blood cells, comparing monocyte amount (shown in green) with other cells.]]

==See also==
* [[Complete blood count]]
* [[Hematopoiesis]]
* [[Lymphocyte]]
* [[Neutrophil granulocyte]]
* [[Phagocyte]]
* [[List of distinct cell types in the adult human body]]

== Further reading ==

* Jakubzick, C. V., Randolph, G. J., & Henson, P. M. (2017). ''Monocyte differentiation and antigen-presenting functions''. In: ''[[Nature Reviews Immunology]]''. {{doi|10.1038/nri.2017.28}}

== References ==
{{Reflist|2}}

==External links==
* {{BUHistology|01702ooa}}
* [http://www.monocyte.eu/ Human Monocytes&nbsp;— Prof. Dr. Ziegler-Heitbrock]
* {{usurped|1=[https://web.archive.org/web/20101222222719/http://www.simplylearnt.com/topic/Circulation-of-Body-Fluids Circulation of Body Fluids]}}

{{Myeloid blood cells and plasma}}
{{Lymphocytic immune system}}
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[[Category:Mononuclear phagocytes]]
[[Category:Immune system]]
[[Category:Cell biology]]
[[Category:Human cells]]