EXPRESSION AND FUNCTION OF ALPHA(4) BETA(7) INTEGRIN ON HUMAN NATURAL-KILLER-CELLS/

In this report, we have analysed the expression and function of the al pha(4)/beta(7) heterodimer in human natural killer (NK) cells. The exp ression of alpha(4) beta(7) is induced in NK cells upon activation, as the anti-alpha(4) beta(7) ACT-1 monoclonal antibody (mAb) faintly sta ined a minority of peripheral blood NK cells, whereas it strongly reac ted with in vitro long-term interleukin-2 (IL-2)-activated NK cells. I ncubation with ACT-1 or its F(ab')(2) fragments induced a strong homot ypic adhesion of NK cells, comparable to that stimulated by the anti-a lpha(4) HP1/7 mAb. Cell-cell interaction induced by the ACT-1 mAb was only prevented by another anti-alpha 4 mAb (HP2/1) that recognizes a d ifferent epitope. In alpha(4)/beta(7)-mediated cell aggregation, the a lpha(4) beta(7) heterodimer was redistributed to intercellular contact sites, thus, suggesting a direct involvement of this integrin in the formation of cell clusters. In NK cells attached to Fibronectin (FN38) or vascular cell adhesion molecule-1 (VCAM-1), both alpha(4) beta(7) and alpha(4) beta(1) integrins were redistributed at the ventral cellu lar membrane forming discrete contact sites. The ACT-I mAb only partia lly blocked NK cell binding to FN38, but in combination with the anti- beta(1) mAb LIA1/2, NK cell binding to FN38 was completely inhibited. In contrast, ACT-I did not modify NK cell adhesion to VCAM-1. thus sup porting the theory that the alpha(4) beta(7) binding sites for both li gands appear to be different. Our results indicate that upon IL-2-acti vation, expression of functional alpha(4)/beta(7), integrin is induced on NK cells, potentially participating in their interaction with both extracellular matrix and endothelial cells.