Disease relevance of ITGAX

• CD11c is a member of the beta(2) integrin family of adhesion molecules that, together with CD18, forms a heterodimeric receptor on the surface of myeloid, NK, dendritic, and certain leukemic, lymphoma, and activated lymphoid cells [1].
• In Crohn's disease ileum, the beta2 integrin mucosal and submucosal expression was similar to normal; however, muscle and adventitial expression was increased, particularly for CD11c [2].
• Mucosal CD11c expression was significantly greater in Crohn's disease than in ulcerative colitis [2].
• In a group of 18 subjects with acute deep venous thrombosis (DVT), evidenced by clinical examination and echo-color-Doppler, we examined the phenotypical expression of the polymorphonuclear leukocyte (PMN) beta2-integrins (CD11a, CD11b, CD11c, CD18), obtained by using a flow cytofluorimeter [3].
• CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD [4].

Psychiatry related information on ITGAX

• Cerebellar amyloid deposits in Alzheimer's disease were studied by immunocytochemistry and with a series of antibodies that recognize human microglia, including anti-HLA-DR, LN-1, Leu-M5 and leukocyte common antigen [5].

High impact information on ITGAX

• We have now identified a subset of CD4+ CD11c+ CD3- dendritic cells in the germinal centres [6].
• The alpha d subunit is more closely related to CD11b and CD11c than to CD11a [7].
• These results demonstrate that CD11b and CD11c are receptors for CD23 and that this novel ligand pairing regulates important activities of monocytes [8].
• Analysis of CD11c-enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual "balloon" shape, varies along the length of the small bowel [9].
• The beta2 family of integrins, CD11a, CD11b, CD11c, and alphad, are expressed on most leukocytes [10].

Chemical compound and disease context of ITGAX

• The results were (1) NO inhalation changed neither the baseline nor the Escherichia coli lipopolysaccharide (LPS)-induced expression of the cell adhesion molecules CD11a, CD11b, CD11c, and CD62L (l-selectin) on neutrophilic granulocytes (PMN) or monocytes (Mo) [11].
• Following challenge of the acute promyelocytic leukemia (APL) cell line, NB4, with 1, 25 dihydroxy vitamin D3 (1, 25 D3), no increase in the expression of the monocytic surface markers, CD11c, CD14 and HLA-DR is observed [12].
• In addition, Bryo 1 treatment induced WSU-CLL cells to become CD11c, CD25 and tartrate-resistant acid phosphatase-positive, specific markers for hairy cell leukemia, a disease exquisitely sensitive to 2-CdA [13].

Biological context of ITGAX

• Monocytic differentiation is associated with an induction of both CD11c and CD18 gene expression [1].
• The resulting CD11c/CD18 receptor mediates firm adhesion to the vascular endothelium, transendothelial migration, chemotaxis, and phagocytosis [1].
• All four myelomonocytic cell lines showed down-regulation of alpha 4 and up-regulation of CD11c after TPA treatment [14].
• LPS-induced stimulation of phagocytosis in the sipunculan worm Themiste petricola: possible involvement of human CD14, CD11B and CD11C cross-reactive molecules [15].
• The two c-jun binding sites in the CD11c promoter were essential for continued expression of CD11c in U937-PKC-zeta cells [16].

Anatomical context of ITGAX

• Unlike other mast cells, UMC expressed CD11c/CD18 (p150,95) and CD32 (Fc gamma RII) [17].
• The leukocyte integrin p150,95 (CD11c/CD18) as a receptor for iC3b. Activation by a heterologous beta subunit and localization of a ligand recognition site to the I domain [18].
• On the other hand, antibodies against CD11b, CD11c, and LB-2 showed only marginal reactivity with highly purified LGL-free T cells [19].
• Recently, we reported that in U937 cells, expression of the CD11c gene is controlled by an unidentified transcription factor that binds ssDNA [1].
• During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter [1].

Associations of ITGAX with chemical compounds

• However, the activation of neutrophils depends on the interaction of CD11c/CD18 with the A alpha-chain of platelet-expressed fibrinogen and the contractile system of neutrophils [20].
• In order to investigate whether binding of fibrinogen to these integrins is involved, monoclonal antibodies (MoAbs) and Gly-Pro-Arg-Pro (GPRP) peptide that inhibits fibrinogen binding to CD11c/CD18 were checked for their effects on the interaction of activated platelets and neutrophils [20].
• Genistein, herbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N'-tetraacetic acid blocked the immediate expression of CD64 in a dose-dependent manner, suggesting that the signal is mediated through calcium mobilization and protein tyrosine kinase(s) [21].
• FACS analysis showed that 1,25-DHCC increased the number of cells expressing CD11b in both DH39 and controls, and the number of cells expressing CD11c in DH39 [22].
• Although AP-1 mediates the responsiveness to several other differentiating agents including GM-CSF, additional elements are required for induction of the CD11c promoter activity upon Sodium Butyrate-triggered differentiation [23].

Physical interactions of ITGAX

• In this study, we report that in U937 cells, expression of the CD11c gene is mediated by the ssDNA-binding protein Puralpha [1].
• We also identified 2 peptides derived from sequences of ICAM-4 that are capable of modulating the binding to CD11c/CD18 [24].
• A soluble fusion protein containing the extracellular domain of ICAM-1 abolished C-GRWSGWPADL-C phage binding to CD11c/CD18 [25].

Regulatory relationships of ITGAX

• During PMA-induced differentiation, the ability of Puralpha to activate the CD11c promoter in U937 cells increases, as does that of Sp1 [1].
• CD64 expression is induced in a slow kinetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents [21].
• Functional inhibition of AP-1 expressed by hairy cells reduced CD11c promoter activity by 80% [4].
• Like all other WSP tested, they induced an upregulation of CD11b but had no influence on CD11c and, most strikingly, CD62L expression [26].
• Moreover, synthetic monomeric circular peptide C-GRWSGWPADL-C bound specifically to CD11c/CD18 and inhibited ICAM-1 binding [25].

Other interactions of ITGAX

• The interaction was specifically inhibited by anti-CD11b or anti-CD11c, respectively, and by anti-CD23 MAbs [8].
• As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05) [27].
• CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells [28].
• MoAbs against CD11c or CD49d had little or no effect [29].
• The expression of CD11c, CD83, and CCR7 in PA-treated NB4 cells was further increased by tumor necrosis factor (TNF)-alpha treatment [30].

Analytical, diagnostic and therapeutic context of ITGAX

• By subcellular fractionation and immunoprecipitation studies, we have found that CD11b, CD11c and CD18 molecules were mainly localized in the membranes of tertiary granules, which were resolved from the specific and azurophilic granules as well as from the plasma membrane fraction [31].
• The presence of CD11a, CD11c and CD18 could be confirmed on a low percentage of normal skin mast cells by immunofluorescence, using a double staining technique [32].
• Recent studies have defined different DC populations, therefore we undertook this study comparing 2 types of myeloid DCs: blood CD11c(+) DCs and in vitro monocyte-derived DCs (Mo-DCs), which are both candidates as cellular adjuvants for cancer immunotherapy [33].
• The expression of CD18, CD11a, CD11b and CD11c on the surface of polymorphonuclear leukocytes was examined by flow cytometry with monoclonal antibodies [34].
• The expression of CD11a and CD11c did not change at any sampling points after PTCA in either of the two patient groups [34].

References