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ng vertebrate eye specific patterning positive regulation of neuron death positive regulation of microglial cell activation positive regulation of microglial cell mediated cytotoxicity cell surface receptor signaling pathway involved in cell cell signaling positive regulation of prostaglandin e synthase activity forebrain development apoptotic signaling pathway positive regulation of hippocampal neuron apoptotic process sources amigo quickgo orthologs databases ncbi entry oma entry species human mouse entrez 3684 16409 ensembl ensg00000169896 ensmusg00000030786 uniprot p11215 p05555 refseq mrna nm_000632 nm_001145808 nm_001082960 nm_008401 refseq protein np_000623 np_001139280 n a location ucsc chr 16 31 26 31 33 mb chr 7 127 66 127 72 mb pubmed search 3 4 wikidata view edit human view edit mouse integrin alpha m itgam is one protein subunit that forms heterodimeric integrin alpha m beta 2 α m β 2 molecule also known as macrophage 1 antigen mac 1 or complement receptor 3 cr3 5 itgam is also known as cr3a and cluster of differentiation molecule 11b cd11b the second chain of α m β 2 is the common integrin β 2 subunit known as cd18 and integrin α m β 2 thus belongs to the β 2 subfamily or leukocyte integrins 6 α m β 2 is expressed on the surface of many leukocytes involved in the innate immune system including monocytes granulocytes macrophages and natural killer cells 5 and subsets of t and b cells 7 it mediates inflammation by regulating leukocyte adhesion and migration and has been implicated in several immune processes such as phagocytosis cell mediated cytotoxicity chemotaxis and cellular activation 5 it is involved in the complement system due to its capacity to bind inactivated complement component 3b ic3b 8 the itgam alpha subunit of integrin α m β 2 is directly involved in causing the adhesion and spreading of cells but cannot mediate cellular migration without the presence of the β2 cd18 subunit 5 in genome wide association studies single nucleotide polymorphisms in itgam had the strongest association with systemic lupus erythematosus with an odds ratio of 1 65 for the t allele of rs9888739 and lupus 9 10 in histopathology immunohistochemistry with antibodies against cd11b is frequently used to identify macrophages and microglia function edit cd11b as an integrin molecule on the surface of leukocytes plays an important role in cell migration adhesion and transmigration across blood vessels because it can bind to components of extracellular matrix and intracellular adhesion molecules icams on the endothelial surface this process is important for leukocyte recruitment into the site of inflammation 7 moreover there are other important processes with cd11b involvement more precisely mac 1 integrin involvement as a whole one of which is phagocytosis of opsonised particles by a complement component ic3b such opsonised particles could be bacteria apoptotic cells and even immune complexes cd11b binding to ic3b leads to a production of anti inflammatory cytokines e g interleukin 10 il 10 and tumour growth factor beta tgfβ this process is important for regulation of the inflammatory milieu 7 11 cd11b is also involved in the differentiation of osteoclasts bone remodelling cells mac 1 is expressed in osteoclast progenitors and it seems that it is a part of a negative feedback of osteoclastogenesis 11 cd11b also modulates other functions of leukocytes e g oxidative burst apoptosis binding of fibrinogen etc 12 on circulating leukocytes cd11b is expressed in a closed conformation the switch into an active conformation follows quickly after the stimulation of toll like receptors tlr of the leukocytes 7 once activated cd11b can bind its ligands with high affinity e g binding of icam 2 molecules on tlr signalling in the cell tlr stimulation results in the production of pro inflammatory cytokines e g il 6 and il 1β via a series of phosphorylation of signalling factors one of which is the nf κb transcription factor 13 this signalling is in fact negatively affected by cd11b signalling consequently this leads to a reduced activation of nf κb and lower production of above mentioned pro inflammatory cytokines to conclude cd11b signalling negatively regulates leukocyte activation after tlr stimulation 7 12 beside tlr signalling cd11b also negatively regulates b cell receptor bcr signalling and it suppresses t cell activation and dendritic cell maturation and function 7 therapeutic significance edit cd11b plays an important role in immune cell regulation once this regulation is disrupted it may lead to a higher susceptibility to inflammatory and autoimmune diseases some examples would be systemic lupus erythematosus sle lupus nephritis and certain types of cancer 12 14 systemic lupus erythematosus edit genome wide association studies helped to uncover three main single nucleotide polymorphisms snps in cd11b that are associated with the risk of developing sle cardiovascular disease and lupus nephritis a complication usually occurring along with sle these snps are rs1143679 r77h rs1143678 p1146s and rs1143683 a858v and they result in the lower ability of cd11b to properly bind ic3b thus decreased cell adhesion and phagocytosis reduced ability to negatively regulate the production of pro inflammatory cytokines il 6 il 1β and tumour necrosis factor α tnfα after tlr stimulation have been also observed in these mutations 12 cd11b plays a protective role during sle and lupus nephritis owing to its anti inflammatory properties lupus nephritis is characterised by the accumulation of immune complexes in kidneys and overall immune infiltration into kidneys which results in renal damage this debilitating complication of sle is associated with the above mentioned mutations in cd11b patients with itgam snps have higher serum levels of interferon type i ifn i which is one of the risk factors for developing sle and lupus nephritis moreover higher levels of other pro inflammatory cytokines il 6 il 1β and tnfα after tlr stimulation observed in patients with itgam snps further drive the inflammation during this disease causing more tissue damage and creation of immune complexes 7 12 hence cd11b represents a possible therapeutic target for the treatment of sle indeed many attempts to target cd11b have been made including antibody based therapy which proved to be ineffective in the case of cd11b 15 however other therapies using small allosteric cd11b agonists seem to be a promising tool as their activation of cd11b leads to a regulation of tlr dependent pro inflammatory pathways and protection from renal damage 12 tumours edit cd11b seems to be a potent player in managing certain types of solid tumours even though nowadays many tools for cancer treatment exist multiple factors of this illness remain a challenging topic one of them are myeloid derived suppressor cells mdsc and tumour associated macrophages tams which are myeloid cells present in the tumour microenvironment possessing suppressor properties thus favouring the tumour growth tams however do not have only tumour promoting properties they can also display tumour inhibiting properties it depends on their stimulation the tumour inhibiting properties include the production of pro inflammatory cytokines and the ability to present antigens 14 using cd11b agonists seems to be of importance in tumour treatment agonist that stabilize cd11b in its active conformation result in higher adhesion of cd11b to its endothelial ligands consequently impair the ability of transendothelial migration to the site of inflammation such agonist therapy is under development and one promising candidate gb1275 is currently in its first clinical phase at the beginning of 2023 this agonist of cd11b shows impaired transmigration of suppressive tams into the site of tams towards pro inflammatory phenotype with higher antigen presentation and production of pro inflammatory cytokines therefore promising better tumour inhibition 14 see also edit integrin references edit 1 2 3 grch38 ensembl release 89 ensg00000169896 ensembl may 2017 1 2 3 grcm38 ensembl release 89 ensmusg00000030786 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine mouse pubmed reference national center for biotechnology information u s national library of medicine 1 2 3 4 solovjov da pluskota e plow ef january 2005 distinct roles for the alpha and beta subunits in the functions of integrin alphambeta2 the journal of biological chemistry 280 2 1336 1345 doi 10 1074 jbc m406968200 pmid 15485828 larson rs springer ta april 1990 structure and function of leukocyte integrins immunological reviews 114 181 217 doi 10 1111 j 1600 065x 1990 tb00565 x pmid 2196220 s2cid 36709941 1 2 3 4 5 6 7 khan sq khan i gupta v 2018 03 15 cd11b activity modulates pathogenesis of lupus nephritis frontiers in medicine 5 52 doi 10 3389 fmed 2018 00052 pmc 5862812 pmid 29600248 arnaout ma todd rf dana n melamed j schlossman sf colten hr july 1983 inhibition of phagocytosis of complement c3 or immunoglobulin g coated particles and of c3bi binding by monoclonal antibodies to a monocyte granulocyte membrane glycoprotein mol the journal of clinical investigation 72 1 171 179 doi 10 1172 jci110955 pmc 1129172 pmid 6874946 crow mk february 2008 collaboration genetic associations and lupus erythematosus the new england journal of medicine 358 9 956 961 doi 10 1056 nejme0800096 pmid 18204099 hom g graham rr modrek b taylor ke ortmann w garnier s et al february 2008 association of systemic lupus erythematosus with c8orf13 blk and itgam itgax the new england journal of medicine 358 9 900 909 doi 10 1056 nejmoa0707865 pmid 18204098 1 2 bednarczyk m stege h grabbe s bros m february 2020 β2 integrins multi functional leukocyte receptors in health and disease international journal of molecular sciences 21 4 1402 doi 10 3390 ijms21041402 pmc 7073085 pmid 32092981 1 2 3 4 5 6 villanueva v li x jimenez v faridi hm gupta v july 2022 cd11b agonists offer a novel approach for treating lupus nephritis translational research 245 41 54 doi 10 1016 j trsl 2022 03 001 pmc 9167730 pmid 35288363 fitzgerald ka kagan jc march 2020 toll like receptors and the control of immunity cell 180 6 1044 1066 doi 10 1016 j cell 2020 02 041 pmc 9358771 pmid 32164908 1 2 3 denardo dg galkin a dupont j zhou l bendell j august 2021 gb1275 a first in class cd11b modulator rationale for immunotherapeutic combinations in solid tumors journal for immunotherapy of cancer 9 8 e003005 doi 10 1136 jitc 2021 003005 pmc 8404448 pmid 34452928 kabanov ds grachev sv prokhorenko ir 2020 11 21 monoclonal antibody to cd14 tlr4 or cd11b impact of epitope and isotype specificity on ros generation by human granulocytes and monocytes oxidative medicine and cellular longevity 2020 5708692 doi 10 1155 2020 5708692 pmc 7700042 pmid 33294123 further reading edit stewart m thiel m hogg n october 1995 leukocyte integrins current opinion in cell biology 7 5 690 696 doi 10 1016 0955 0674 95 80111 1 pmid 8573344 todd rf petty hr may 1997 beta 2 cd11 cd18 integrins can serve as signaling partners for other leukocyte receptors the journal of laboratory and clinical medicine 129 5 492 498 doi 10 1016 s0022 2143 97 90003 2 pmid 9142045 schymeinsky j mócsai a walzog b august 2007 neutrophil activation via beta2 integrins cd11 cd18 molecular mechanisms and clinical implications thrombosis and haemostasis 98 2 262 273 doi 10 1160 th07 02 0156 pmid 17721605 s2cid 41094726 v t e pdb gallery 1bho mac 1 i domain magnesium complex 1bhq mac 1 i domain cadmium complex 1idn mac 1 i domain metal free 1ido i domain from integrin cr3 mg2 bound 1jlm i domain from integrin cr3 mn2 bound 1m1u an isoleucine based allosteric switch controls affinity and shape shifting in integrin cd11b a domain 1mf7 integrin alpha m i domain 1n9z integrin alpha m i domain mutant 1na5 integrin alpha m i domain external links edit integrin alpham at the u s national library of medicine medical subject headings mesh mouse cd antigen chart human cd antigen chart itgam link removed info with links in the cell migration gateway archived 2014 12 11 at the wayback machine v t e complement system pathways c l a activators enzymes early c c1 c1q c1r c1s c4 c4a c4b c2 l masp1 masp2 mbl a factor b factor d factor p properdin middle c3 c3a c3b ic3b c5 c5a c5b c3 convertase c5 convertase late mac c5b c6 c7 c8 c9 inhibitors cla c1 inhibitor decay accelerating factor cd59 factor i cl c4bp a factor h complement receptors cr1 cr2 cr3 cr4 cd11b cd11c cd18 anaphylatoxin c3a c5a function cytotoxicity by mac immune adherence inducing inflammation opsonization category commons v t e proteins clusters of differentiation see also list of human clusters of differentiation 1 50 1 a c 1a 1b 1d 1e 2 3 γ δ ε 4 5 6 7 8 a 9 10 11 a b c d 13 14 15 16 a b 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 a b 33 34 35 36 37 38 39 40 41 42 a b c d 43 44 45 46 47 48 49 a b c d e f 50 51 100 51 52 53 54 55 56 57 58 59 61 62 e l p 63 64 a b c 66 a b c d e f 68 69 70 71 72 73 74 78 79 a b 80 81 82 83 84 85 a d e h j k 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 150 101 102 103 104 105 106 107 a b 108 109 110 111 112 113 114 115 116 117 118 119 120 a b 121 a b 122 123 124 125 126 127 129 130 131 132 133 134 135 136 137 138 140b 141 142 143 144 146 147 148 150 151 200 151 152 153 154 155 156 a b c 157 158 a d e i k 159 a c 160 161 162 163 164 166 167 a b 168 169 170 171 172 a b g 174 177 178 179 a b 180 181 182 183 184 185 186 191 192 193 194 195 196 197 w198 w199 200 201 250 201 202b 204 205 206 207 208 209 w210 a b 212 213a 1 2 217 218 a b 220 221 222 223 224 225 226 227 228 229 230 233 234 235 a b 236 238 239 240ce 240d 241 243 244 246 247 248 249 251 300 252 253 254 256 257 258 261 262 263 264 265 266 267 268 269 271 272 273 274 275 276 278 279 280 281 282 283 284 286 288 289 290 292 w293 294 295 297 298 299 301 350 300a 301 302 303 304 305 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hidden categories articles with short descr...