MACROPHAGE-COLONY-STIMULATING FACTOR INDUCES THROMBOSPONDIN-1 PRODUCTION BY CULTURED HUMAN MACROPHAGES

The role of colony-stimulating factors (CSFs) in regulating the synthe sis of thrombospondin 1 (TSP1) by cultured human macrophages is invest igated. Macrophage (M)-CSF is shown rapidly and transiently to induce two predominant species of TSP1 mRNA. One of these species was 3.2 kb in size and appeared to be specific to M-CSF-stimulated macrophages. A dherent M-CSF-treated macrophages are also shown to express abundant s urface cell-associated TSP rapidly when examined by indirect immunoflu orescence staining. Granulocyte-macrophage (CM)-CSF induced TSP1 mRNA at a later time point, and this was attributable to the effects of end ogenous M-CSF induced by the CM-CSF; the CM-CSF-treated cells did not display surface-associated TSP after 3 hr of treatment. Analysis of th e TSP1 protein synthesised by the M-CSF-treated macrophages revealed t he expected trimeric form of the molecule. In addition, an unidentifie d 95-kDa protein was found to be covalently associated with immunoreac tive TSP1, and this appeared to be specific to the macrophages as it w as not found in TSP1 precipitated from other cell types. It is suggest ed that the induction of TSP1 by M-CSF may play an important role in t he major physiological functions of macrophages. (C) 1995 Wiley-Liss, Inc.