Disease relevance of ITGA5

• VLA-5 integrin was found on a relatively small number (26%) of mature B cell leukemias [1].
• These results indicate that VLA-5 on monocytes serves as a receptor for FimD on B. pertussis [2].
• Treatment with TGF-beta1 of stroma from multiple myeloma BM samples produced a substantial increase in VLA-5 use by the myeloma cell line NCI-H929 to adhere to this stroma [3].
• Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5 [4].
• Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6 [4].

High impact information on ITGA5

• The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration [5].
• This paper shows that the common VLA beta-subunit is equivalent to subunits found in structures with known fibronectin and laminin receptor activity, and that VLA-3 and VLA-5 are similar or identical to these previously defined receptors for adhesion molecules [6].
• Migration requires the engagement of VLA4 in cooperation with VLA5 and both receptors regulate the persistence and directionality of movement [7].
• Herein, we show that the cytokines interleukin (IL)-3, granulocyte-macrophage CSF (GM-CSF), and KIT ligand (KL) are physiological activators of VLA-4 and VLA-5 expressed by MO7e, TF1, and normal bone marrow CD34+ progenitor cells [8].
• The VLA-5 fibronectin receptor was mainly expressed on CD4+ CD45R-CDw29+ cells and may in part contribute to the unique function of these cells [9].

Chemical compound and disease context of ITGA5

• These results demonstrate that interaction of FimD of B. pertussis with VLA-5 on monocytes activates CR3, which requires protein tyrosine kinases and results in enhanced binding of B. pertussis to the latter receptor via FHA [2].
• We studied the surface expression of CXCR4 very late activation antigen (VLA)-4 and VLA-5 on myeloma cells mobilized with cyclophosphamide and GM-CSF in 12 multiple myeloma patients undergoing HSC mobilization for autologous transplantation [10].

Biological context of ITGA5

• In addition, a remarkable induction was detected in the genes for syndecan-4 (SDC4) and alpha5-integrin (ITGA5), the cell-adhesion molecules involved in the enhanced adhesion of cancer cells to fibronectin [11].
• ITGB1 was assigned to Chromosome (Chr) 19, ITGA4 to Chr 3, and ITGA5 to Chr 7 [12].
• We confirm that the integrins very late antigen (VLA)-4 and VLA-5 are expressed on the CD34+ cell lines MO7e, TF1, and on normal bone marrow CD34+ progenitor cells, but in a low affinity state, conferring on them a weak adhesive phenotype on fibronectin (Fn) [8].
• CC chemokines induced early activation and subsequent deactivation of VLA-4, whereas upregulation of VLA-5 avidity occurred later and persisted [13].
• Nevertheless, anti-alpha 5 MoAb completely inhibited chemotaxis when it was added with anti-alpha 4 in FR4ds, demonstrating a novel complementary role of VLA-5 toward VLA-4 in the chemotaxis induced by FN [14].

Anatomical context of ITGA5

• Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments [15].
• In the binding assays, the numbers of FDCs bound to fibronectin- and laminin-coated dishes and LFs of cryostat sections of human tonsils were reduced markedly by pretreatment with monoclonal antibodies against CD29, CD49e, and CD49f [16].
• Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules [17].
• These mast cells were found to express VLA (very late Ag)-3 (75.3 +/- 35.6 specific fluorescence intensity) and, to lesser degree, VLA-4 and VLA-5 receptors (8.0 +/- 2.5 and 6.9 +/- 3.2 specific fluorescence intensity, respectively) [18].
• IL-6 also enhanced the fluorescence intensity of beta 1 integrins, CD49d, CD49e, and CD49f, expressed on NK cells [19].

Associations of ITGA5 with chemical compounds

• Treating monocytes with purified, 120-kDa cell-binding FN fragments (FN120) likewise decreased VLA-5 expression, and did so by inducing a serine proteinase-dependent proteolysis of this beta(1) integrin [15].
• Abs to the beta(1) integrins, CD49d and CD49e, as well as to P-selectin and P-selectin glycoprotein ligand 1, inhibited basophil rolling and adhesion [20].
• Down-modulation of VLA-5 on the apical surface of monocytes by plating the cells onto surfaces precoated with anti-VLA-5 mAb also inhibited binding of beads coated with maltose-binding protein-FimD to monocytes, while precoating of the surfaces with mAb against VLA-6 or CR3 had no effect [2].
• These results indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin on the PMN cell surface, primarily the VLA-5 integrin [21].
• The tyrosine phosphorylation of polypeptides of 130 kDa and 77 kDa was triggered in U-937 cells by the interaction of FN with the VLA-5 receptor in a high-affinity conformation [22].

Physical interactions of ITGA5

• Analysis of binding mechanisms indicated that very late antigen-4 (VLA-4) and VLA-5 were responsible for AML cell binding to fibronectin [23].
• K562 lacked VLA-4 and a low binding affinity of the VLA-5 on these cells resulted in an absence of binding to the bone-marrow stroma [24].

Regulatory relationships of ITGA5

• A monoclonal antibody (mAb) against CD49e blocked the adhesion of both types of moDC to FN [25].
• Signal transduction through the beta1 integrin family surface adhesion molecules VLA-4 and VLA-5 of human B-cell precursors activates CD19 receptor-associated protein-tyrosine kinases [26].
• Combined cell cycle and phenotypic analysis showed that the expression of VLA-5 was upregulated during S/G2+M but that of VLA-4 remained constant [27].
• Pretreatment of cells with integrin antagonists such as RGD-containing peptide and antibody against very late antigen-5 (VLA-5) inhibited the up-regulation of ICAM-1 expression, suggesting the participation of VLA-5 integrin in this response [28].
• Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism [29].

Other interactions of ITGA5

• Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration [15].
• The majority of leukemic blasts studied expressed CD49d and CD49e as well [30].
• Immunoelectron microscopy revealed fibers surrounded by cytoplasmic FDC extensions that were CD29-, CD49e-, and CD49f-positive [16].
• High surface expression of CD49e, CD51, and CD61 along with kit was apparent by 4 weeks of culture, whereas expression of each at day 0 was low to undetectable [31].
• Using a panel of specific antibodies we showed that freshly harvested human epidermal basal cells express VLA-2 and VLA-3 receptors, a low amount of VLA-5, but fail to express VLA-4 [32].

Analytical, diagnostic and therapeutic context of ITGA5

• By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent [33].
• The presence of VLA-4 as well as VLA-5 on activated eosinophils was confirmed by demonstration of the formation of immune rosettes using antibody-coated microspheres and by their attachment to fibronectin-coated surfaces [34].
• Negative staining was obtained with antibodies to the fibronectin receptor VLA-5 and VLA-3 [35].
• All tumors exhibiting weak or strong positive staining for VLA4 or VLA5 showed extrarenal invasion or were known to have developed metastases at the time of nephrectomy [36].
• On unexposed sites, cells from old donors showed a significantly increased adhesion capacity on collagen (plus 50.7%) and on fibronectin (plus 62.4%) and an increased staining pattern of VLA 2 and VLA 5 integrins in immunohistochemistry in comparison with young donors [37].

References