Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis.

Abstract

SummaryAdhesion molecules are probably required for retention of maturing lymphocyte precursors in bone marrow, where they closely interact with and are dependent on stromal cells . Lymphomyeloid cell lines avidly adhere to cloned stromal cell lines in culture and screening pairs of these resulted in a selection strategy for a new monoclonal antibody to a leukocyte adhesion molecule. Immunoprecipitation analyses and comparison to a previously described antibody showed that it recognizes the a4 chain of the integrin, VLA 4. This antibody totally inhibited lymphopoiesis and retarded myelopoiesis in long-term bone marrow cultures. A similar selection strategy resulted in two additional antibodies which define a single 100-kD species on stromal cells. This stromal cell adhesion molecule is a potential counter-receptor/ligand for VLA4 on murine Lmpho-myeloid cells . Our findings suggest a new role for VLA-4 in lymphoid progenitor-microenvironment interactions. Recognition molecules that function in cell migration and inflammation in peripheral tissues may be important for steady-state lymphopoiesis within bone marrow.

In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for α5, αv, and α4 Integrins

“…Integrin receptors have been suggested to be important in regulating these processes. ␣ 5 , ␣ V , and ␣ 4 integrins recognize different sites on fibronectin, and they also bind other specific ligands, including vitronectin for ␣ V integrins and VCAM-1 and mucosal addressin cell adhesion molecule-1 (MAd-CAM-1) 6 for ␣ 4 integrins (2,3). Expression studies have shown the presence of integrins on leukocyte progenitors and their differential regulation among lineages (1,4).…”

“…The functions of integrin receptors during leukocyte development in vivo, however, have been unclear. In vitro studies have previously suggested that ␣ 4 integrins participate in B lymphocyte and myeloid development (6,7). The expression of ␣ 4 and ␣ 5 integrins on thymocytes is finely regulated, and this has also suggested a role for these receptors during T lymphocyte differentiation (8).…”

Culture system for extensive production of CD19+IgM+ cells by human cord blood CD34+ progenitors

“…Comparison of cell-cell contact and cell-cell noncontact culture systems for B cell development It has been reported that cell-cell interactions between stroma and progenitor cells play important roles in early Blymphopoiesis in both murine 11,[27][28][29][30][31] and human [32][33][34][35] systems. Therefore, to elucidate whether cell-cell interactions between MS-5 cells and progenitor cells are required for the generation of CD19 + cells in our culture, CD34 + cells were cultured with or without the 0.45 m microporous filter on an MS-5 cell layer.…”

Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma

“…23 A similar mechanism may occur in human myeloma in which aberrant expression of IL-1␤ induces increased expression of adhesion molecules such as VLA-4, CD44, CD54, CD56, and other surface molecules on the monoclonal plasma cells. [24][25][26][27][28] The etiology of acquired IL-1␤ expression in myeloma is unknown. However, the IL-1␤ gene is highly inducible and its expression can be affected by many microbial and cellular products.…”