Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity

Abstract

Current ideas about the mechanism of wound healing and the pathogenesis of atherosclerosis, pulmonary fibrosis and hepatic fibrosis suggest a central role for the mononuclear phagocyte in attracting and/or stimulating the proliferation of mesenchymal cells. We demonstrate here that activated human blood monocytes, but not resting monocytes, release a mediator that attracts smooth muscle cells and cooperates with other mediators to stimulate fibroblast proliferation. This mediator is very similar to platelet-derived growth factor (PDGF): its chromatographic properties and chemical stability are similar to those of PDGF, it competes with 125I-PDGF for binding to fibroblasts and it immunoprecipitates with anti-PDGF antibodies. In parallel, stimulated monocytes, but not resting monocytes, express the c-sis proto-oncogene, a gene coding for one of the PDGF chains, consistent with the concept that expression of the c-sis proto-oncogene may be involved in the ability of mononuclear phagocytes to modulate the accumulation of mesenchymal cells.

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid

“…It is well established that PDGF is produced by macrophages (Martinet et al, 1985); accumulation of such cells could explain the finding. Since neuronal cells are sources of PDGF (Sasahara et al, 1991;Yeh et al, 1991) it is not surprising to find measurable amounts of PDGF in other types of non-neoplastic lesions.…”

Macrophages and tumor angiogenesis

“…28 Also VEGF is chemotactic for monocytes via VEGFR-1. 29,30 TAM expresses and releases epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), 31,32 transforming growth factor-a and -b (TGF-a and -b), [33][34][35] VEGF, 36 TNF-a 37 IL-1, 38 IL-6, IL-8, 39 platelet-activating factor 40 platelet-derived growth factor (PDGF) 41 G-CSF and GM-CSF. 42 thymidine phosphorylase 43 and chemokines, such as CCL2.…”

DNase‐I‐hypersensitive sites located far upstream of the human c‐sis/PDGF‐B gene comap with transcriptional enhancers and a silencer and are preceded by (part of) a new transcription unit

“…This suggests that PDGF B could also play a role in the etiology and/or maintainance of epithelial tumors in vivo. c-sis mRNA is expressed in a variety of normal cells, such as placental cytotrophoblasts (Goustin et al, 1985), activated monocytes (Martinet et al, 1986), vascular endothelial cells (DiCorleto and Bowen-Pope, 1983) and smooth muscle cells (Seifert et al, 1984). Blood platelets, from which PDGF was originally purified, lack transcriptional machinery.…”