Effetti delle piastrine e dei leucociti sulla proliferazione delle cellule muscolari in vitro: ruolo dei mediatori chimici di derivazione piastrinica.

Some evidence indicate that platelets (PLTs) and leukocytes might contribute to the development of neointimal hyperplasia following arterial injury, via release of several growth factors. To study the relative contribution of these cells and of growth factors released in consequence of activation, smooth muscle cells (SMCs), isolated from the aorta of New Zealand White rabbits, were grown in Dulbecco's medium containing 10% fetal calf serum (FCS). At 70% confluence, SMCs were made quiescent by removing FCS from the medium. Twenty-four hours later, the cells were stimulated with activated platelets, neutrophils, lymphocytes+monocytes, whole leukocytes and platelets + whole leukocytes. Then, 1 microCi of O3H-thymidine were added to SMC cultures to evaluate the degree of proliferation. Relative contribution of different PLT-derived mediators to SMC growth was evaluated by adding either ketanserin, a 5-HT2 receptor antagonist, ridogrel, a thromboxane A2 (TxA2) receptor antagonist, BN52021, a platelet activating factor (PAF) receptor antagonist, and trapidil, a platelet-derived growth factor (PDGF) receptor antagonist, or all antagonists together. SMC proliferation was significantly increased by platelet activation. This effect was reduced by adding either ketanserin, ridogrel, BN 52021 or trapidil. Neutrophils, lymphocytes + monocytes and whole leukocytes also increased SMC proliferation. Simultaneous stimulation of SMCs by platelets and whole leukocytes was associated with a significant increase in SMC proliferation as compared to platelets or leukocytes alone. Thus, TxA2, 5-HT, PAF, and PDGF all contribute to SMC proliferation in vitro. Adding all antagonist together resulted in an additive antiproliferative effect. Leukocytes are also important in SMC proliferation. Interaction between platelets and leukocytes may play a pivotal role in the modulation of this phenomenon.