Monocytes are a type of leukocyte or white blood cell . They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells . As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
29-530: TREM1 , a triggering receptor expressed on myeloid cells 1, a human gene TREM2 , a triggering receptor expressed on myeloid cells 2, a human gene Trem Desportivo Clube Trem da Alegria , children musical band in Brazil Trem das Onze , classical samba composition by Brazilian singer Adoniran Barbosa Tremulous , a popular free and open source FPS video game. Trace rare-earth element The highest point of
58-440: A cell that has recently phagocytized foreign matter. 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 vesicles for processing foreign material. Although they can be derived from monocytes,
87-468: A diameter of 15–22 μm , monocytes are the largest cell type in peripheral blood . Monocytes are mononuclear cells and the ellipsoidal nucleus is often lobulated/indented, causing a bean-shaped or kidney-shaped appearance. Monocytes compose 2% to 10% of all leukocytes in the human body. Monocytes are produced by the bone marrow from precursors called monoblasts , bipotent cells that differentiated from hematopoietic stem cells . Monocytes circulate in
116-597: A large proportion is already formed prenatally in the yolk sac and foetal liver. In vitro , monocytes can differentiate into dendritic cells by adding the cytokines granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 . 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. Aside from their differentiation capacity, monocytes can also directly regulate immune responses. As explained before, they are able to perform phagocytosis. Cells of
145-729: Is an immunoglobulin (Ig) superfamily transmembrane protein that, in humans, is encoded by the TREM1 gene . TREM1 is constitutively expressed on the surface of peripheral blood monocytes and neutrophils, and upregulated by toll-like receptor (TLR) ligands; activation of TREM1 amplifies immune responses. Monocyte -, macrophage - and neutrophil -mediated inflammatory responses can be stimulated via receptors such as G protein-linked 7-transmembrane receptors (such as FPR1 ), Fc receptors , CD14 , TLRs (such as TLR4 ), and cytokine receptors. TREM1 amplifies TLR-induced inflammation by increasing production of inflammatory cytokines. The ligand of TREM1
174-566: Is being evaluated in a phase 1 trial , in combination with pembrolizumab , in subjects with advanced solid tumors Celsius Therapeutics is developing CEL383, an antibody inhibitor of TREM1, for treatment of inflammatory bowel disease. As of October 2023, CEL383 is being evaluated in a phase 1 trial in healthy volunteers. Monocyte Monocytes are amoeboid in appearance, and have nongranulated cytoplasm . Thus they are classified as agranulocytes , although they might occasionally display some azurophil granules and/or vacuoles . With
203-455: 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. The absence of non-classical monocytes can assist in diagnosis of the disease and the use of slan as a marker can improve specificity. Monocytopenia is a form of leukopenia associated with a deficiency of monocytes. A very low count of these cells
232-446: Is different from Wikidata All article disambiguation pages All disambiguation pages TREM1 1Q8M , 1SMO 54210 58217 ENSG00000124731 ENSMUSG00000042265 Q9NP99 Q9JKE2 NM_001242589 NM_001242590 NM_018643 NM_021406 NM_001347399 NP_001229518 NP_001229519 NP_061113 NP_001334328 NP_067381 Triggering receptor expressed on myeloid cells 1 (TREM1)
261-746: Is enriched on myeloid subsets, including mMDSCs, TANs, TAMs ( AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics 2021 abstract no. P104 ). Single-cell immune profiling of stage III-C ovarian tumor specimens revealed that TREM1 is specifically expressed in TAM and monocytes in these tumors ( AACR-NCI-EORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS 2019 abstract no. C105 ). Additional studies found high expression of TREM1 protein and TREM1 mRNA, respectively, in TAMs and monocytes in human tumors ( Immunotherapy of Cancer Conference (ITOC) 2021 Abstract P02.11 , Society for
290-465: Is higher in tumor vs non-tumor tissues, likely due to its expression by myeloid cells that infiltrate tumors. TREM1 is expressed by myeloid immune-suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC), tumor-associated neutrophils (TANs), and tumor associated macrophages (TAMs). These types of tumor-associated myeloid infiltrate correlate with shorter survival times of patients with solid tumors, and are likely to be
319-405: Is initiated, activating downstream mediators such as PLCγ , PI3K , and MAPK . This cascade promotes the release of inflammatory cytokines and/or chemokines by neutrophils and macrophages, as well as their migration. Based on laboratory studies, TREM1 might be involved in development of atherosclerosis , non-alcoholic fatty liver disease ( NAFLD ), and ischemic stroke . TREM1 expression
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#1732851499565348-417: Is unknown, however, bacterial infection, ischemic stroke and challenge with lipopolysaccharide or lipoteichoic acid were observed to increase TREM1 expression. In granulocytes, C/EBPε induces TREM1 expression independently from inflammatory response. TREM1 forms a complex with transmembrane adaptor DAP12 and, upon TREM1 engagement, a protein tyrosine kinase Syk -mediated cascade of tyrosine phosphorylation
377-730: The Suva Planina mountain range in Serbia Trem (village) , a village in Hitrino Municipality , Shumen Province , Bulgaria. Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title Trem . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=Trem&oldid=1047015770 " Category : Disambiguation pages Hidden categories: Short description
406-534: The chemotaxis and other functions of monocytes. These factors include most particularly chemokines such as monocyte chemotactic protein-1 (CCL2) and 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 family of OXE1 receptor agonists (e.g., 5-HETE and 5-oxo-ETE); and N-Formylmethionine leucyl-phenylalanine and other N-formylated oligopeptides which are made by bacteria and activate
435-573: The formyl peptide receptor 1 . Other microbial products can directly activate monocytes and this leads to production of pro-inflammatory and, with some delay, of anti-inflammatory cytokines . Typical cytokines produced by monocytes are TNF , IL-1 , and IL-12 . 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
464-411: The "intermediate" subset is specifically enriched in the bone marrow. In mice, monocytes can be divided in two subpopulations. Inflammatory monocytes ( CX3CR1 , CCR2 , Ly6C , PD-L1 ), which are equivalent to human classical CD14 CD16 monocytes and resident monocytes ( CX3CR1 , CCR2 , Ly6C , PD-L1 ), which are equivalent to human non-classical CD14 CD16 monocytes. Resident monocytes have
493-464: The Immunotherapy of Cancer (SITC) Conference 2021, Poster 859 ). Higher levels of TREM1 mRNA in tumor tissues correlate with shorter survival times of patients with colon cancer , breast cancer , pancreatic cancer , and squamous cell carcinoma ( AACR-NCI-EORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS 2019 abstract no. C105 ). During inflammation, a soluble form of
522-497: The ability to patrol along the endothelium wall in the steady state and under inflammatory conditions. Monocytes are mechanically active cells 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
551-414: The bloodstream for about one to three days and then typically migrate into tissues throughout the body where they differentiate into macrophages and dendritic cells . 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. Today, three types of monocytes are recognized in human blood: While in humans
580-442: 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 cytokines like tumor necrosis factor and interleukin-12 after stimulation with microbial products. Furthermore, a monocyte patrolling behavior has been demonstrated in humans both for
609-576: The classical and the non-classical monocytes, meaning that they slowly move along the endothelium to examine it for pathogens. Said et al. showed that activated monocytes express high levels of PD-1 which might explain the higher expression of PD-1 in CD14 CD16 monocytes as compared to CD14 CD16 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. Many factors produced by other cells can regulate
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#1732851499565638-429: 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. 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
667-694: The immune response. Pionyr Immunotherapeutics is developing PY159 for treatment of advanced solid tumors refractory to or relapsed with the current standard of care. PY159 is a humanized monoclonal antibody that binds TREM1 and acts as an agonist, crosslinking TREM1 to induce signaling through the TREM1-DAP12 complex ( SITC 2019 Poster P812 , AACR-NCI-EORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS 2019 abstract no. C-105 , AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics 2021 Abstract P104 , ITOC 2021 Abstract P02.11 , SITC 2021 Poster 859 ). PY159
696-609: 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 ( opsonising ) proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern recognition receptors that recognize pathogens. Monocytes are also capable of killing infected host cells via antibody-dependent cell-mediated cytotoxicity . Vacuolization may be present in
725-586: 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. 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
754-464: The molecule (sTREM1) accumulates in the circulation, and is a biomarker of inflammation. There is debate over whether sTREM1 is produced as a splice variant or as the results of proteolytic cleavage. sTREM1 acts as a decoy for the unknown TREM1 ligands, and thereby prevents TREM1 activation. sTREM1 has been studied as a biomarker of development of pneumonia, sepsis, inflammatory bowel diseases, and liver cirrhosis. Model organisms have been used in
783-507: The reason that not all tumors respond to checkpoint inhibitor therapy. Antibodies that target TREM1 are therefore being studied for use in treatment patients with tumors that do not respond to checkpoint inhibitor therapy. Flow cytometric analyses of human tumor-infiltrating myeloid cells isolated from breast cancer, bladder cancer, endometrial cancer, head and neck squamous cell carcinoma, ovarian cancer, prostate cancer, and renal cell carcinoma tissues demonstrated that within tumors, TREM1
812-554: The severity and disease progression in COVID-19 patients. 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: A high count of CD14 CD16 monocytes is found in severe infection ( sepsis ). In the field of atherosclerosis, high numbers of the CD14 CD16 intermediate monocytes were shown to be predictive of cardiovascular events in populations at risk. CMML
841-482: The study of TREM1 function. A conditional knockout mouse line called Trem1 was generated at the Wellcome Trust Sanger Institute . Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens included immune phenotyping. Blockade of TREM1 protects mice against microbe-induced shock, indicating that it is an important regulator of
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