EXPRESSION AND FUNCTION OF FIBRONECTIN-BINDING INTEGRINS ON RAT MAST-CELLS

Adhesion molecules of the integrin family are implicated not only in l eukocyte migration but also in leukocyte activation. Here we character ize the expression and function of fibronectin receptor integrins on r at mast cells. A rat basophilic leukemia cell line (RBL-2H3) and phorb ol ester-stimulated rat peritoneal mast cells adhered to fibronectin ( FN), vitronectin and fibrinogen. These mast cells expressed fibronecti n receptor integrins, including very tate antigen (VLA)-4, VLA-5 and v itronectin receptor (VNR), as estimated by immunofluorescent staining and inhibition of FN adherence by newly established mAbs reactive with the rat alpha 4 (MR alpha 4-1), alpha 5 (HM alpha 5-1) or beta 3 (HM beta 3-1) chains of the integrin molecules. The beta-hexosaminidase re lease, a marker for mast cell degranulation, triggered by high affinit y lgE receptor (Fc epsilon RI)-mediated stimulation, was enhanced by a dhesion of RBL-2H3 cells to either immobilized FN, MR alpha 4-1, HM al pha 5-1 or HM beta 3-1. This FN enhancement of beta-hexosaminidase rel ease was inhibited by soluble MR alpha 4-1, HM alpha 5-1 and HM beta 3 -1 as well as by GRGDSP and DELPQLVTLPHPNHLGPEILDVPST peptides which a brogate VLA-5/VNR and VLA-4 binding to FN respectively. In vivo, passi ve cutaneous anaphylaxis induced by lgE anti-DNP and DNP-BSA was inhib ited by concurrent s.c. injection of MR alpha 4-1, HM alpha 5-1 and HM beta 3-1. These results demonstrate that FN receptor integrins expres sed on rat mast cells play an important role in regulating mast cell a ctivation both in vitro and in vivo.