Genomes and Genes
Gene Symbol: Itgam
Description: integrin alpha M
Alias: CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40, MAC1, Mac-1, Mac-1a, integrin alpha-M, CD11 antigen-like family member B, CD11B (p170), CR-3 alpha chain, Mac-1 alpha, cell surface glycoprotein MAC-1 alpha subunit, cell surface glycoprotein MAC-1 subunit alpha, complement component receptor 3 alpha-a, complement receptor type 3, leukocyte adhesion receptor MO1, macrophage antigen alpha
- Eberl G, Marmon S, Sunshine M, Rennert P, Choi Y, Littman D. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol. 2004;5:64-73 pubmed..This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues. ..
- Hadas S, Reichert F, Rotshenker S. Dissimilar and similar functional properties of complement receptor-3 in microglia and macrophages in combating yeast pathogens by phagocytosis. Glia. 2010;58:823-30 pubmed publisher..Complement receptor-3 (CR3) has initially been implicated in mediating the phagocytosis of both C3bi-op and non-opsonized (nop) zymosan by MO ..
- Kanwar S, Smith C, Shardonofsky F, Burns A. The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice. Am J Respir Cell Mol Biol. 2001;25:170-7 pubmedMac-1 (CD11b/CD18) is an important adhesion molecule involved in the migration of leukocytes, cell signaling, and subsequent secretory responses. Its precise role in eosinophil recruitment and activation in vivo is not entirely clear...
- Soriano S, Coxon A, Wang Y, Frosch M, Lipton S, Hickey P, et al. Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke. 1999;30:134-9 pubmedMacrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte beta2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic ..
- Kumar S, Xu J, Perkins C, Guo F, Snapper S, Finkelman F, et al. Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules. Blood. 2012;120:3563-74 pubmed publisher..In our previous report, we suggested that Rho GTPase Cdc42 controls neutrophil polarity through CD11b signaling at the uropod, albeit through an unknown mechanism...
- Han C, Jin J, Xu S, Liu H, Li N, Cao X. Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b. Nat Immunol. 2010;11:734-42 pubmed publisher..However, the interaction between integrin alpha(M) (CD11b), which has high expression in monocytes and macrophages, and Toll-like receptor (TLR)-triggered innate immunity ..
- Scott M, Billiar T. Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes. J Biol Chem. 2008;283:29433-46 pubmed publisher..We find that essential components for LPS uptake are CD14, TLR4, MD2, and the beta2-integrin CD11b/CD18...
- Bullard D, Hu X, Schoeb T, Axtell R, Raman C, Barnum S. Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. J Immunol. 2005;175:6327-33 pubmedMac-1 (CD18/CD11b) is a member of the beta2-integrin family of adhesion molecules and is implicated in the development of many inflammatory diseases...
- Perera P, Mayadas T, Takeuchi O, Akira S, Zaks Zilberman M, Goyert S, et al. CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J Immunol. 2001;166:574-81 pubmed..Recent reports indicate that three membrane-associated proteins, CD14, CD11b/CD18, and Toll-like receptor (TLR) 4, may serve as LPS recognition and/or signaling receptors in murine ..
- Hirahashi J, Mekala D, Van Ziffle J, Xiao L, Saffaripour S, Wagner D, et al. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity. 2006;25:271-83 pubmed..These data suggest that Mac-1 engagement of complement activates tyrosine kinases to promote elastase-dependent blood vessel injury in vivo. ..
- Rotshenker S, Reichert F, Gitik M, Haklai R, Elad Sfadia G, Kloog Y. Galectin-3/MAC-2, Ras and PI3K activate complement receptor-3 and scavenger receptor-AI/II mediated myelin phagocytosis in microglia. Glia. 2008;56:1607-13 pubmed publisher..myelin through phosphatidylinositol-3-kinase (PI3K)-dependent phagocytosis mediated by complement receptor-3 (CR3/MAC-1) and scavenger receptor-AI/II (SRAI/II)...
- Gao X, Liu Q, Broman M, Predescu D, Frey R, Malik A. Inactivation of CD11b in a mouse transgenic model protects against sepsis-induced lung PMN infiltration and vascular injury. Physiol Genomics. 2005;21:230-42 pubmedTo inactivate chronically the beta2-integrin CD11b (Mac-1), we made a transgenic model in mice in which we expressed the CD11b antagonist polypeptide neutrophil inhibitory factor (NIF)...
- Szczur K, Zheng Y, Filippi M. The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling. Blood. 2009;114:4527-37 pubmed publisher..Interestingly, Cdc42 makes use of the integrin CD11b during this process. Cdc42 determines the redistribution of CD11b at the uropod...
- Kevil C, Hicks M, He X, Zhang J, Ballantyne C, Raman C, et al. Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease. Am J Pathol. 2004;165:609-16 pubmed..These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE. ..
- Shimizu K, Libby P, Shubiki R, Sakuma M, Wang Y, Asano K, et al. Leukocyte integrin Mac-1 promotes acute cardiac allograft rejection. Circulation. 2008;117:1997-2008 pubmed publisher..Although the leukocyte integrin Mac-1 (alpha(Mbeta2), CD11b/CD18) facilitates cell-cell interactions among leukocytes and interactions between leukocytes and endothelial ..
- Melo M, Catchpole I, Haggar G, Stokes R. Utilization of CD11b knockout mice to characterize the role of complement receptor 3 (CR3, CD11b/CD18) in the growth of Mycobacterium tuberculosis in macrophages. Cell Immunol. 2000;205:13-23 pubmedUsing CD11b knockout mice as a source of macrophages (Mphi;), we show that complement receptor 3 (CR3) mediates approximately 40-50% of nonopsonic binding and 50-60% of serum-mediated binding of Mycobacterium tuberculosis to resident ..
- Hidalgo A, Chang J, Jang J, Peired A, Chiang E, Frenette P. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med. 2009;15:384-91 pubmed publisher..These results indicate that endothelial selectins can influence neutrophil behavior beyond its canonical rolling step through delayed, organ-damaging, polarized activation. ..
- Lu H, Smith C, Perrard J, Bullard D, Tang L, Shappell S, et al. LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice. J Clin Invest. 1997;99:1340-50 pubmedTo better define the specific function of Mac-1 (CD11b) versus LFA-1 (CD11a) and the other CD11 integrins in vivo, we have disrupted murine CD11b by targeted homologous recombination in embryonic stem cells and generated mice which are ..
- Coxon A, Rieu P, Barkalow F, Askari S, Sharpe A, von Andrian U, et al. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity. 1996;5:653-66 pubmedIn mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced...
- Van Ziffle J, Lowell C. Neutrophil-specific deletion of Syk kinase results in reduced host defense to bacterial infection. Blood. 2009;114:4871-82 pubmed publisher..These results indicate that loss of Syk kinase-mediated integrin signaling impairs leukocyte activation, leading to reduced host defense responses. ..
- Cao C, Lawrence D, Strickland D, Zhang L. A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics. Blood. 2005;106:3234-41 pubmed
- Watts G, Beurskens F, Martin Padura I, Ballantyne C, Klickstein L, Brenner M, et al. Manifestations of inflammatory arthritis are critically dependent on LFA-1. J Immunol. 2005;174:3668-75 pubmed..Blocking mAbs further revealed an ongoing requirement for LFA-1 I-domain adhesive function in disease perpetuation. These findings suggest that the LFA-1 I-domain forms an attractive target for treatment of human inflammatory arthritis. ..
- Tang T, Rosenkranz A, Assmann K, Goodman M, Gutierrez Ramos J, Carroll M, et al. A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis. J Exp Med. 1997;186:1853-63 pubmed..Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice. ..
- Jongstra Bilen J, Harrison R, Grinstein S. Fcgamma-receptors induce Mac-1 (CD11b/CD18) mobilization and accumulation in the phagocytic cup for optimal phagocytosis. J Biol Chem. 2003;278:45720-9 pubmedFunctional interactions between Fcgamma-receptors (FcgammaR) and the beta2 integrin Mac-1 (CD11b/CD18) have been described, but the molecular basis of this relationship remains unclear...
- Brown G, Taylor P, Reid D, Willment J, Williams D, Martinez Pomares L, et al. Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med. 2002;196:407-12 pubmed..Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the beta-glucan ..
- Ding Z, Babensee J, Simon S, Lu H, Perrard J, Bullard D, et al. Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J Immunol. 1999;163:5029-38 pubmed..Neutrophil extravasation in response to TNF-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased. ..
- Zhou H, Liao J, Aloor J, Nie H, Wilson B, Fessler M, et al. CD11b/CD18 (Mac-1) is a novel surface receptor for extracellular double-stranded RNA to mediate cellular inflammatory responses. J Immunol. 2013;190:115-25 pubmed publisher..The present study demonstrated that CD11b/CD18 (Mac-1 [macrophage-1 Ag]), a surface integrin receptor, recognized extracellular dsRNA and induced macrophage ..
- Sumagin R, Prizant H, Lomakina E, Waugh R, Sarelius I. LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ. J Immunol. 2010;185:7057-66 pubmed publisher..Using function-blocking Abs, we show that these different crawling patterns were due to CD11a/CD18 (LFA-1)- versus CD11b/CD18 (Mac-1)-mediated crawling...
- Menezes G, Lee W, Zhou H, Waterhouse C, Cara D, Kubes P. Selective down-regulation of neutrophil Mac-1 in endotoxemic hepatic microcirculation via IL-10. J Immunol. 2009;183:7557-68 pubmed publisher..This may be a mechanism to keep neutrophils in sinusoids for intravascular trapping. ..
- Levesque S, Taetzsch T, Lull M, Johnson J, McGraw C, Block M. The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function. J Neurochem. 2013;125:756-65 pubmed publisher..However, pre-treatment with the MAC1/CD11b inhibitor antibody blocked microglial H2 O2 production in response to DEP...
- Gao H, Zhou H, Zhang F, Wilson B, Kam W, Hong J. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci. 2011;31:1081-92 pubmed publisher..high-mobility group box 1), released from inflamed microglia and/or degenerating neurons, bound to microglial Mac1 (macrophage antigen complex 1) and activated nuclear factor-ÎºB pathway and NADPH oxidase to stimulate production ..
- Simon D, Dhen Z, Seifert P, Edelman E, Ballantyne C, Rogers C. Decreased neointimal formation in Mac-1(-/-) mice reveals a role for inflammation in vascular repair after angioplasty. J Clin Invest. 2000;105:293-300 pubmed..markers of leukocyte activation - in particular, increased expression of the beta2-integrin Mac-1 (alphaMbeta2, or CD11b/CD18), which is responsible for firm leukocyte adhesion to platelets and fibrinogen on denuded vessels - predict ..
- Henneke P, Takeuchi O, Malley R, Lien E, Ingalls R, Freeman M, et al. Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways. J Immunol. 2002;169:3970-7 pubmed..and elimination of bacteria, occur through a coordinated engagement of TLRs, along with the coreceptors CD14 and CD11b/CD18...
- Wang Y, Bugatti M, Ulland T, Vermi W, Gilfillan S, Colonna M. Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation. Eur J Immunol. 2016;46:552-9 pubmed publisher..Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes. ..
- Liu Z, Zhao M, Li N, Diaz L, Mayadas T. Differential roles for beta2 integrins in experimental autoimmune bullous pemphigoid. Blood. 2006;107:1063-9 pubmed..Wild-type (WT) mice pretreated with neutralizing antibody against CD11a (LFA-1), CD11b (Mac-1), CD11a plus CD11b, or CD18 alone failed to develop BP when injected with pathogenic anti-mBP180 IgG...
- McClellan S, Jerome A, Suvas S, Hazlett L. NLRC4 regulates caspase-1 and IL-1beta production in a CD11blowLy6Glow population of cells required for resistance to Pseudomonas aeruginosa keratitis. PLoS ONE. 2017;12:e0185718 pubmed publisher..These data provide evidence that the NLRC4 inflammasome contributes to resistance through regulation of caspase-1, IL-1beta and IL-18 in a CD11blowLy6Glow population of cells. ..
- Taylor P, Chu C, Plater Zyberk C, Maini R. Transfer of type II collagen-induced arthritis from DBA/1 to severe combined immunodeficiency mice can be prevented by blockade of Mac-1. Immunology. 1996;88:315-21 pubmed..Our findings support the hypothesis that cells expressing Mac-1 play an important role in the induction and maintenance of joint damage in collagen-induced arthritis. ..
- Veenstra A, Tang J, Kern T. Antagonism of CD11b with neutrophil inhibitory factor (NIF) inhibits vascular lesions in diabetic retinopathy. PLoS ONE. 2013;8:e78405 pubmed publisher..Leukocyte integrin ?m?2 (CD11b/CD18, MAC1), a protein mediating adhesion, has been shown to mediate damage to endothelial cells by activated ..
- Zhou Q, Ho A, Schlitzer A, Tang Y, Wong K, Wong F, et al. GM-CSF-licensed CD11b+ lung dendritic cells orchestrate Th2 immunity to Blomia tropicalis. J Immunol. 2014;193:496-509 pubmed publisher..tropicalis extract induces strong Th2 priming in the lung draining lymph node. Resident CD11b(+) dendritic cells (DCs) preferentially transport Ag from the lung to the draining lymph node and are crucial for ..
- Hadas S, Spira M, Hanisch U, Reichert F, Rotshenker S. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin. J Neuroinflammation. 2012;9:166 pubmed publisher..Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3) is a principal phagocytic receptor in myelin phagocytosis...
- Qi C, Cai Y, Gunn L, Ding C, Li B, Kloecker G, et al. Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived ?-glucans. Blood. 2011;117:6825-36 pubmed publisher..These findings reveal the importance of different preparations of ?-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials. ..
- Zen K, Guo Y, Li L, Bian Z, Zhang C, Liu Y. Cleavage of the CD11b extracellular domain by the leukocyte serprocidins is critical for neutrophil detachment during chemotaxis. Blood. 2011;117:4885-94 pubmed publisherThe ?(2)-integrin CD11b/CD18 mediates the firm adhesion of neutrophils (PMNs) to epithelial monolayers, a key step in PMN transepithelial migration...
- Daito H, Kikuchi T, Sakakibara T, Gomi K, Damayanti T, Zaini J, et al. Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells. Eur Respir J. 2011;38:688-701 pubmed publisher..Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+ CD11c+ cells (dendritic cells) through TLR9 signalling...
- Hajishengallis G, Wang M, Liang S. Induction of distinct TLR2-mediated proinflammatory and proadhesive signaling pathways in response to Porphyromonas gingivalis fimbriae. J Immunol. 2009;182:6690-6 pubmed publisher..The delineation of these signaling pathways may provide appropriate targets for selectively inhibiting or enhancing specific activities, depending on whether they undermine or promote the host defense. ..
- Rosenkranz A, Mayadas T. Leukocyte-endothelial cell interactions - lessons from knockout mice. Exp Nephrol. 1999;7:125-36 pubmed..Second, we discuss models of experimental glomerulonephritis and what we have learned about leukocyte adhesion receptors in the pathogenesis of glomerulonephritis through studies in knockout mice. ..
- Rosenzweig H, Kawaguchi T, Martin T, Planck S, Davey M, Rosenbaum J. Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN-gamma. Invest Ophthalmol Vis Sci. 2009;50:1739-45 pubmed publisher..Mice deficient in IFN-gamma, NOD2, or CD11b and their wild-type controls were treated with intravitreal injection of MDP in the presence or absence of IFN-..
- Waffarn E, Hastey C, Dixit N, Soo Choi Y, CHERRY S, Kalinke U, et al. Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation. Nat Commun. 2015;6:8991 pubmed publisher..In vivo trafficking experiments identify CD11b as the non-redundant, interferon-activated integrin required for B-1 cell accumulation in MedLNs...
- Lundberg Y, Cabrera R, Greer K, Zhao J, Garg R, Finnell R. Mapping a chromosomal locus for valproic acid-induced exencephaly in mice. Mamm Genome. 2004;15:361-9 pubmed..These results suggest a major chromosomal locus associated with the sensitivity to VPA-induced exencephaly in mice. ..
- Barbour T, Ling G, Ruseva M, Fossati Jimack L, Cook H, Botto M, et al. Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy. Kidney Int. 2016;89:823-32 pubmed publisher..Here we show that deficiency of complement receptor 3 (CR3), the main receptor for iC3b, enhances the severity of spontaneous renal disease in Cfh(-/-) mice...
- Ong L, Tan H, Feng C, Qu J, Loh S, Bhattacharyya S, et al. The Systemic Lupus Erythematosus-Associated Single Nucleotide Polymorphism rs1143678 in Integrin ?M Cytoplasmic Tail Generates a 14-3-3? Binding Site That Is Proinflammatory. J Immunol. 2017;198:883-894 pubmed publisher..Genome-wide association studies have identified several ITGAM (?M subunit) single nucleotide polymorphisms that are associated with systemic lupus erythematosus...
- Makarenkova V, Bansal V, Matta B, Perez L, Ochoa J. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176:2085-94 pubmed..We describe that myeloid suppressor cells expressing CD11b(+)/Gr-1(+) markers invade the spleen after traumatic stress and suppress T cell function through the production of ..