DIFFERENTIAL UTILIZATION OF VLA-4 (ALPHA-4-BETA-1) AND VLA-5 (ALPHA-5-BETA-1) INTEGRINS DURING THE DEVELOPMENT OF MOUSE BONE-MARROW-DERIVEDMAST-CELLS

Cytokines have been shown to have major roles in the development of ma st cells from bone marrow progenitors. Immature mast cells derived fro m bone marrow thus leave the blood system to complete their course of maturation within tissues. However, it is now clear that VLA (beta 1) integrins with function in mediating cell-cell and cell-extracellular matrix protein interactions have effects on the growth and differentia tion of diverse cell types. At present, the involvement of VLA integri ns during mast cell development is still unclear. In this study, we re port the preparation of a new monoclonal antibody (mAb) against mouse VLA-5 (alpha 5 beta 1) integrin. Together with mAb R1-2, we characteri zed the expression of VLA-4 (alpha 4 beta 1) and VLA-5 integrins, the two major fibronectin receptors, on two long-term cultured mast cell l ines, CFTL-15 and MC/9. 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. We speculated that VLA integrin expression may be related to mast c ell development. Thus bone marrow-derived mast cells (BMMC) were chara cterized after varying periods of development induced by IL-3. During the first 3 weeks the expression of VLA-4 and VLA-5 increased progress ively and both were involved in mediating adhesion of BMMC to fibronec tin. At time periods of greater than 3 weeks, the expression of VLA-4 declined gradually to little, if any, by week 13. In comparison, VLA-5 remained stably expressed and functioned as the major receptor for fi bronectin. Results from this study therefore suggest that BMMC differe ntially utilize VLA-4 and VLA-5 integrins during IL-3-induced developm ent. Differential expression of VLA integrins may have effects on the recirculation properties, tissue distribution and eventual maturation of progenitors to fully matured mast cells.