Cross-linking of alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors enhances natural killer cell cytotoxic activity.

摘要: Cell/extracellular matrix interactions mediated by integrins regulate differentiation, migration, and effector functions of immune system components. Human NK cells express alpha 4 beta 1 5 integrins, which mediate their binding to fibronectin (FN). We have investigated the ability FN its integrin receptors modulate cytotoxicity. Our data show that presence immobilized significantly augments spontaneous cytotoxic activity in vitro cultured human against several NK-susceptible, but not NK-resistant, target cells; Ab-dependent cytotoxicity Ab-coated P815 redirected lysis anti-CD16 hybridomas are also enhanced FN. Solid-phase-bound anti-human 1, or F(ab')2 fragment, anti-alpha mAbs, all consistently enhance murine cells. The 120-kDa (alpha 1-binding), 40-kDa fragment fully reproduced enhancing effect observed with entire molecule. demonstrate cross-linking on induces an increase intracellular Ca2+ concentration is abrogated EGTA, thus suggesting capacity mobilize involved coactivating role