Contraction-dependent apoptosis of normal dermal fibroblasts

The mechanisms underlying the contraction-dependent apoptosis of primary fi broblasts are of prime importance in understanding anchorage-dependent surv ival/apoptosis of dermal fibroblasts. As integrins are essential extracellu lar matrix receptors in fibroblasts, their role in anchorage-dependent apop tosis/ survival of fibroblasts was analyzed. Primary human fibroblasts disp layed a marked reduction of apoptosis in mechanically relaxed collagen matr ices in the presence of adhesion-blocking antibodies against alpha (1)beta (1) or alpha (2)beta (1). Anti-alpha (v)beta (3) antibodies had a considera bly weaker effect. In additional experiments RD cells, which lack alpha (2) integrin, displayed no apoptosis in mechanically relaxed collagen matrices . Their susceptibility to apoptosis was restored after transfection with fu nctional alpha (2) integrin, and it could be blocked again by adhesion-bloc king antibodies against alpha (2)beta (1) integrin. Therefore we conclude t hat apoptosis of human primary fibroblasts in contractile collagen matrices is - at least in part - inhibited by adhesion-blocking anti-integrin antib odies, suggesting that the mode of apoptosis in this case is different from anoikis. Further, apoptosis in a mechanically relaxed collagen matrix coul d be abrogated by depolymerization of F-actin using cytochalasin D and also by disturbing actin-myosin interaction using 2,3-butanedione monoxime, ind icating a possible dependence of apoptosis on mechanical forces and/or cell shape.