Disease relevance of Itga5

• Analysis of levels of expression comparing resting peritoneal macrophages with macrophages elicited using inflammatory stimuli indicated that alpha chain message and surface VLA-5 expression were significantly increased using thioglycollate or Listeria monocytogenes as stimuli to elicit cells [1].
• Requirement for VLA-4 and VLA-5 integrins in lymphoma cells binding to and migration beneath stromal cells in culture [2].
• The adhesion of anti-CD3-stimulated T cells to syngeneic MCA-38 mouse colon adenocarcinoma cells did not involve LFA-1 (alpha(L)beta(2)) or VLA-5 (alpha(5)beta(1)) [3].
• Consequently, the CH-296 fragment can enhance GT through binding to both retrovirus particles and target cells that express integrins VLA-5 and/or VLA-4 [4].
• These results strongly suggest that intrahepatic metastasis of CBO140C12 tumors is partly due to the marked invasive and adhesive abilities of tumor cells mediated by expression of MMP-9 and integrin alpha3beta1 (VLA-3), integrin alpha5beta1 (VLA-5) on the tumor surface, respectively [5].

High impact information on Itga5

• Moreover, macrophage clearance into lymphatics can be blocked in vivo by RGD peptides and VLA-4 and VLA-5 but not beta(2) blocking antibodies [6].
• We observed that macrophage-mesothelial adhesion is Arg-Gly-Asp (RGD) sensitive and partially mediated by very late antigen (VLA)-4 and VLA-5 but not alpha(v) or beta(2) integrins [6].
• These results indicate that macrophage VLA-5 expression can be modulated in vivo and may provide an important mechanism by which macrophages are recruited to or adhere to fibronectin in inflammatory foci [1].
• Molecular cloning of a murine fibronectin receptor and its expression during inflammation. Expression of VLA-5 is increased in activated peritoneal macrophages in a manner discordant from major histocompatibility complex class II [1].
• Human fibronectin receptor (VLA-5) alpha and beta chain probes were used to identify their mouse homologues in a thioglycollate-elicited peritoneal exudate cell cDNA library [1].

Biological context of Itga5

• The fibronectin receptor, alpha subunit (Itga5) maps to murine chromosome 15, distal to D15Mit16 [7].
• The more potent compounds were highly selective and did not affect U937 cell adhesion to fibronectin (VLA-5), phorbolmyristate acetate or PMA-differentiated U937 cell adhesion to intercellular cell adhesion molecule-1 (ICAM-1)-expressing Chinese hamster ovary cells (LFA-1) and adenosine diphosphate (ADP)-induced platelet aggregation (GPIIb/IIIa) [8].
• Together with our previous work, these results indicate that, upon ingestion of fibronectin-bound S. aureus, VLA-5 accumulates in the area of phagocytosis in inflammatory macrophages, where it forms adhesion complexes [9].
• To show a role for EF-hands of different proteins in VLA-5-mediated adhesion, we used calcium-like peptides (CALP), CALP1 and CALP2, designed to bind to EF-hands based on inverted hydropathy [10].
• The more potent compounds were highly selective and did not affect U937 cell adhesion to fibronectin (VLA-5), PMA-differentiated U937 cell adhesion to intercellular cell adhesion molecule- 1-expressing Chinese hamster ovary cells (LFA-1) and ADP-induced platelet aggregation (GPIIb/IIIa) [11].

Anatomical context of Itga5

• Here we show that the expression of VLA-5 is restricted to thioglycolate-induced inflammatory macrophages and is not found in the resident macrophages [9].
• Finally, Tpo stimulated adhesion of primitive (CD34+ CD38-) human bone marrow cells to fibronectin, predominantly through activation of VLA-5, whereas no such effect could be observed on CD34+ CD38+ bone marrow cells [12].
• However, this cell line did not express classical FN receptors such as very late antigen (VLA)-4 and VLA-5, as estimated by immunofluorescent staining [13].
• Immunohistochemical studies revealed that the integrins VLA 3, VLA 5 and integrin receptors to vitronectin are expressed in the epithelium and/or mesenchyme during the glandular stage of murine lung development [14].
• We conclude that CALP1 and 2 can inhibit VLA-5-mediated adhesion of mast cells to fibronectin through binding to EF-hands of multiple proteins, and that these peptides can be used as lead compounds for the development of future therapy against allergy [10].

Associations of Itga5 with chemical compounds

• Furthermore, the enhancing effect by FN was inhibited in the presence of the Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) peptide but not in the presence of the connecting segment-1 (CS-1) peptide, suggesting that enhancement of AICD observed in CD4+ CD8+ thymocytes is mediated through VLA-5 [15].
• Our results suggest a novel binding pathway, in which the VLA-5 integrin binds to L1 on adjacent cells [16].
• No inhibition was found with antibodies against glycoprotein IIb:IIIa, against the alpha 2 chain of VLA-2, and against the alpha 5 chain of VLA-5 [17].
• Ligand-binding affinity of VLA-5 was also augmented by receptor tyrosine kinases when the phospholipase Cgamma-1/protein kinase C pathway was inhibited [18].
• Expression of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133(+) cells was not modified by imatinib, but imatinib decreased the ability of CD133(+) cells to migrate [19].

Physical interactions of Itga5

• Previous studies have shown the presence of several cation-binding domains in VLA-5 that are homologous to the calcium-binding EF-hands of calmodulin [10].

Regulatory relationships of Itga5

• They adhered to fibronectin through VLA-5 when stimulated with steel factor and also directly to membrane-anchored steel factor through c-kit [20].
• The IEC adhesion to FN was inhibited by specific antibody against the FN receptor (VLA-5), as well as competitive Arg-Gly-Asp (RGD) peptide [21].
• 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 [22].
• In monocytic ESb-MP cells the molecule serves as a ligand for P-selectin and triggering with CD24 specific antibodies can activate VLA-5/L1-mediated cell adhesion in these cells [23].

Other interactions of Itga5

• Herein, we investigated the expression of receptors for fibronectin [very late antigen (VLA)-4 and VLA-5] and laminin (VLA-6), known to play a role in thymocyte migration [24].
• VLA-4 was predominantly expressed at the CD4- CD8- stage, and thereafter the expression was reduced, whereas VLA-5 was constantly expressed during maturation [15].
• This adhesion occurs to the same extent as that triggered by optimal levels of Steel factor (SF) or IgE + antigen (IgE + Ag) and is mediated by an increased avidity of the integrin very late antigen 5 (VLA-5) [25].
• Interestingly only CALP2 was able to inhibit Mn(2+)-induced calmodulin-independent adhesion by interfering with an extracellular target, which is probably VLA-5 [10].
• In this study, we report the preparation of a new monoclonal antibody (mAb) against mouse VLA-5 (alpha 5 beta 1) integrin [22].

Analytical, diagnostic and therapeutic context of Itga5

• The expression of FN receptor VLA-5 on IECs was examined by flow cytometry [21].

References