Disease relevance of Itga4

• In both subsets, the arrest on VCAM-1 was dependent on high affinity VLA-4 and the homing of these cells to the BM of NOD/SCID was VLA-4-dependent [1].
• This study demonstrates that SFV infection induces the expression of adhesion molecules within the CNS and that VLA-4 plays an important role in the development of inflammation and demyelination in the CNS following SFV infection [2].
• Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation [3].
• Among a series of adhesion molecules, expression of integrin alpha 4 beta 1 showed a unique inverse correlation with the invasive potential of B16 melanoma cell lines [3].
• Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells [4].

High impact information on Itga4

• Anti-CD81 can activate integrin alpha 4 beta 1 (VLA-4) on B cells, facilitating their adhesion to tonsilar interfollicular stroma [5].
• We demonstrate that the lymphocyte integrin alpha 4 beta 7, also implicated in homing to PP, is a receptor for MAdCAM-1 [6].
• These patterns suggest that VLA-4-VCAM-1 interactions influence alignment of secondary myoblasts along primary myotubes and/or the fusion of secondary myoblasts [7].
• We provide evidence that an integrin (VLA-4) and its counter receptor (VCAM-1) have a role in secondary myogenesis [7].
• Both receptors are synthesized by cultured muscle cells: VLA-4 is induced as myotubes form, whereas VCAM-1 is present on myoblasts and myotubes [7].

Chemical compound and disease context of Itga4

• Transfectants of the B cell lymphoma 38C13 were generated that differ exclusively in the expression of integrin beta 1 or beta 7 subunits allowing for a functional comparison of lymphocyte Peyer's patch HEV adhesion molecule 1 (LPAM-1) (alpha 4 beta 7) and very late antigen 4 (VLA-4) (alpha 4 beta 1) in an identical cellular environment [8].
• RESULTS: Early treatment with anti-VLA-4 mAb from days 5-13 showed a significant effect on renal function, with a reduction in albuminuria (p < 0.01) and a higher creatinine clearance (p < 0.05) [9].
• A nonpeptidyl small molecule antagonist, compound A, to nonactivated very late antigen-4 (VLA4) was examined in lung inflammation induced by a single dose of ovalbumin challenge [10].

Biological context of Itga4

• However, blocking VLA-4 or vascular cell adhesion molecule 1 (VCAM-1) had no effect on cell adhesion [11].
• Differentiation of neutrophils induced by granulocyte colony-stimulating factor was accompanied with down-regulation of VLA-4 [12].
• These results support the hypothesis that up-regulation of VLA-4 is important for effector T cell homing to sites of inflammation [13].
• Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4 [14].
• Further, in vitro adhesion of activated peripheral blood cells to CNS blood vessels was abrogated by anti-VLA-4 antibodies that also inhibited cell migration into the CNS of T. cruzi-infected mice [15].

Anatomical context of Itga4

• MAdCAM-1 binds the lymphocyte homing receptor for Peyer's patches, the integrin alpha 4 beta 7 [16].
• These results suggest that migration of cytotoxic T cells into noninflamed tissues is independent of their activation state and does not require L-selectin, LPAM-1, CD2, and VLA-4 [17].
• The adhesion molecules CD2, CD8, CD54, L-selectin, and CD49d (VLA-4 and LPAM-1 alpha-chain) were not expressed by all CTL hybridomas and therefore not indispensable for invasion in vitro and dissemination in vivo [17].
• By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration [18].
• We have investigated the contribution of integrin alpha 4 beta 7 to human peripheral blood eosinophil adhesive interactions [19].

Associations of Itga4 with chemical compounds

• Integrin alpha4beta1 (VLA-4) expression and activity in retinal and peripheral neurons [20].
• However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca(2+)-, Mg(2+)-independent, LFA-1/ICAM-1-, CD2/LFA-3, VLA-4/VCAM-1-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment [21].
• Furthermore, constitutive LFA-1 and VLA-4 expression on T-cells was not affected by PGE1 [22].
• The VLA-4 (alpha 4 beta 1) integrin is a leukocyte glycoprotein involved in both cell-extracellular matrix and cell-cell interactions [23].
• Flow cytometric analysis revealed increased expression of CD11b and VLA-4 on leukocytes attached to platelets after allergen exposure, and CD11b expression on leukocytes was suppressed in thrombocytopenic mice but was restored with the transfusion of FSPs, but not FUSPs, a phenomenon concurrent with the formation of platelet-leukocyte complexes [24].

Physical interactions of Itga4

• Fibronectin binding was mediated via alpha4beta1 integrin (VLA-4), which is expressed at high levels on thymocytes [25].

Regulatory relationships of Itga4

• VCAM-1 is an immunoglobulin (Ig) superfamily member expressed in endothelial cells that mediates adhesion to a variety of leukocytes in a VLA-4 dependent manner [26].
• Using cells fluorescently labelled with the lipophilic dye DiI, myelin basic protein (MBP)-specific CD4 lymphocytes that expressed low or high levels of very late antigen-4 (VLA-4) and non-antigen-specific activated splenocytes homed to mouse brain in similar quantities 2 h after adoptive transfer [27].
• Tc2 and Tc0 had decreased surface VLA-4 density and deficient activation-induced LFA-1/ICAM-1-dependent homotypic adhesion in vitro [28].
• Antibodies to integrin alpha 4 inhibit spreading of WEHI 231 cells on V+ fibronectin [29].
• CFTL-15 cells were found to express both VLA-4 and -5 integrins whereas MC/9 cells expressed only VLA-5 but not VLA-4 [30].

Other interactions of Itga4

• To identify the importance of VLA-4, CD44, ICAM-1 and MAC-1 in the pathogenesis of SFV infection, monoclonal antibodies that block these adhesion molecules were administered in vivo during infection [2].
• However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1 [31].
• Infiltrated eosinophils and mononuclear cells in the skin expressed Mac-1 (eosinophils: 38.9 +/- 1.55%, mononuclear cells: 51.2 +/- 2.15%), LFA-1 (eosinophils: 33.3 +/- 0.95%, mononuclear cells: 23.1 +/- 1.07%) and VLA-4 (eosinophils: 14.3 +/- 1.6%, mononuclear cells: 17.2 +/- 1.38%) at 12 h [32].
• This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM [1].
• Role of very-late antigen-4 (VLA-4) in myelin basic protein-primed T cell contact-induced expression of proinflammatory cytokines in microglial cells [33].

Analytical, diagnostic and therapeutic context of Itga4

• Immunoprecipitation from single-chain-antibody-transfected cells showed that the single-chain antibody was complexed with the integrin alpha 4 and beta 1 subunits, and the diminished sizes of alpha 4 and beta 1 were consistent with impaired maturation [34].
• Very late antigen-4 (VLA-4) and leucocyte function-associated antigen-1 (LFA-1) expression on transferred lymphocytes was measured with flow cytometry [35].
• Blockade of integrin VLA-4 prevents inflammation and matrix metalloproteinase expression in a murine model of accelerated collagen-induced arthritis [36].
• CONCLUSIONS: Prolonged VLA-4 blockade reduces leukocyte recruitment and neointimal growth following air desiccation injury in ApoE (-/-) mice [37].
• Examination of cell adhesion molecule profiles by immunofluorescence flow cytometry has revealed high levels of CD44, moderate levels of VLA-4 and low levels of LFA-1 on all B9-series cells [38].

References