Hemolysate induces tyrosine phosphorylation and collagen-lattice compaction in cultured fibroblasts

Hemolysate, a proposed causative agent for cerebral vasospasm after subarac hnoid hemorrhage, produces contraction of cerebral arteries by activation o f tyrosine kinases. In addition, hemolysate increases fibroblast-collagen c ompaction that could play a role in cerebral vasospasm. We studied the effe ct of hemolysate on tyrosine phosphorylation and fibroblast-collagen compac tion in cultured canine basilar and human dermal fibroblasts using tyrosine kinase inhibitors and tyrosine antibodies. Hemolysate enhanced tyrosine ph osphorylation of two proteins, 64 and 120 kDa, in cultured canine basilar a rtery and human dermal fibroblast cells. The effect of hemolysate was time- dependent and concentration-dependent. Oxyhemoglobin and ATP, the two major components of hemolysate, produced similar tyrosine phosphorylation, howev er, with a different time course. Tyrosine kinase inhibitors genistein and tyrphostin A51 abolished the effect of hemolysate in both cerebral and derm al fibroblasts. Hemolysate increased fibroblast-populated collagen-lattice compaction and tyrosine kinase inhibitors genistein and tyrphostin A51 atte nuated the effect of hemolysate. We conclude that hemolysate activates tyro sine kinase that leads to the increase of fibroblast compaction. This effec t of hemolysate may contribute to cerebral vasospasm. (C) 1999 Academic Pre ss.