Monocyte synthesis of thrombospondin

Monocytes produce thrombospondin (TSP), a trimeric glycoprotein whose primary function is not yet clear. Platelet-poor monocytes (less than 1 platelet/50 monocytes) cultured with [35S]methionine produced [35S] TSP barely detectable by immunoprecipitation with either monoclonal or polyclonal antibody to TSP. Platelet-poor monocytes that had not been so thoroughly depleted of platelets (6-12 platelets/50 monocytes) synthesized readily detectable amounts of [35S] TSP. Addition of increasing numbers of washed platelets to platelet-poor monocytes resulted in increasing synthesis of [35S]TSP. This monocyte-platelet interaction was specific for cell type; neither neutrophils nor red cells could substitute for platelets. The induction of synthesis was specific for TSP; monocyte synthesis of three other proteins was not induced upon the addition of platelets. Platelet lysate or thrombin-induced platelet releasate could not substitute for intact platelets. In fact, platelet lysate inhibited [35S]TSP synthesis by monocyte-platelet cultures. This inhibition was not due to endotoxin contamination, interference with immunoprecipitation, or dilution of the [35S]methionine pool. Platelets required contact with monocytes to exert their effect, as culturing the cell populations with a filter between them prevented increased [35S]TSP synthesis. Monocyte-platelet interactions may serve to specifically increase monocyte synthesis of the adhesive protein, TSP.