Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering

Abstract

. Integrins are heterodimeric cell surface proteins that mediate both cell-cell and cell-extracellular matrix interactions . We and others recently identified cDNAs encoding a novel integrin ß subunit, 07, in lymphocytes . We have now detected 07 mRNA in mouse TK-1 T lymphoma cells, which are known to express the putative Peyer's patch homing receptor a4ßP. We used an anti-peptide antiserum and a novel mAb against the 07 subunit to show that TK-1 cells express 07 as the only subunit associated with a4. We conclude that 07 and ßP are identical. We also show that activated peripheral blood T cells express a4ß7.We studied the function of a4ß7/a4ßP in TK-1 cells, which do not express very late antigen (VLA)-4 (a4ß1) . Cells adhered to intact fibronectin and to a fibronectin fragment containing the CS-1 region, but not to a T HE ability to interact with a variety of cells or with proteins of the extracellular matrix is crucial for a variety of leukocyte functions, including cell activation, phagocytosis, recruitment to sites of inflammation, recirculation, and homing (for reviews see Stoolman, 1989;Butcher, 1990;Springer, 1990). Many adhesion molecules expressed on T lymphocytes belong to the integrin family. Integrins are noncovalently linked heterodimers consisting of an a and a ß subunit that mediate cell-extracellular matrix as well as cell-cell interactions (Hynes, 1987;Ruoslahti, 1991) . The a and ß subunits each have a large extracellular domain, a short transmembrane region, and a cytoplasmic tail. At least 13 different a and eight different ß subunits have been identified to date; these combine to produce at least 18 different integrin heterodimers . Both a and ß subunits participate in the determination ofligand specificity. The tripeptide RGD (Arg-Gly-Asp) is the recognition site for many of the integrins that bind to extracellular matrix proteins.Members of the 01 integrin subfamily (a1ß1 to a6ß1), also referred to as the very late antigens (VLA-1 to VLA-6), bind and mediate adhesion to several extracellular matrix proteins such as laminin, collagens, and fibronectin (Hemler, 1990) .

β1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

“…One possibility is that the b 7 integrins, a E b 7 and a 4 b 7 , compensate for the lack of b 1 expression on these cells. Indeed, a 4 b 7 shares ligands with a 4 b 1 [23,24], and the expression of a 4 on b 1 -IEL strongly suggests that a 4 b 7 is expressed by these cells. In this respect it will be of considerable interest to compare the IEL compartments of b 7 -, b 1 -, and b 7 -b 1 -double-knockout BM chimeras.…”

Differential adhesion pattern of B cell chronic lymphocytic leukemia cells

“…[33][34][35] Each component of this complex independently regulates the activation, proliferation and function of B cells 18,36 and is able to initiate homotypic and heterotypic adhesion. [37][38][39] Aggregation of B cells could also be triggered by other cell surface molecules. 40 Our finding that homotypic adhesion of B-CLL cells was induced only by anti-CD19 and not by mAbs against other B cell antigens indicated, in contrast, that CD19 may have a unique role in initiating aggregation of B-CLL cells.…”

Role of MAdCAM-1 and Its Ligand on the Homing of Transplanted Hematopoietic Cells in Irradiated Mice

“…With α 4 β 7 integrin blockade, in BMC-transplanted mice, homing cells were markedly decreased in the spleen and bone marrow, whereas homing cells were unchanged in SCC-transplanted mice. The MAdCAM-1/α 4 β 7 integrin pathway regulates lymphocyte tethering and rolling on ECs of lymphoid tissues [4,5,34]. Katayama et al reported that α 4 β 7 integrin plays a key role in the initial steps of tethering and rolling but was not required for firm adhesion in the bone marrow microvasculature.…”