Human monocyte modulation of endothelial cells and fibroblast growth: possible mechanism for fibrosis

Several human diseases are characterized by vascular pathology, fibroblast activation, and excessive fibrosis (e.g., scleroderma, chronic graft versus host disease, pulmonary fibrosis). An intense inflammatory exudate of mononuclear cells which are derived from the peripheral blood precedes the vascular and fibrotic changes. We examined, in vitro, the effects of human peripheral blood mononuclear cell culture supernatants (PBM-SN) on the growth and survival of human endothelial cells (EC) and of human dermal fibroblasts (FB). The same PBM-SN consistently induced inhibition of EC and stimulation of FB proliferation. PBM-SN derived from 42 patients with scleroderma induced 32 +/- 5% (mean +/- SE) more inhibition of EC and 42 +/- 18% more stimulation of FB compared with PBM-SN derived from 30 healthy subjects. Depletion of phagocytic cells or adherent cells from PBM resulted in SN with no demonstrable activity on either EC or FB. Partial purification of PBM-SN on ion exchange and gel filtration chromatography revealed the presence of two fractions that stimulated and one fraction that inhibited FB proliferation, and two fractions that inhibited and one that stimulated EC proliferation. These data suggest that monocytes are capable of releasing mediators that stimulate or suppress EC or FB. However, when activated by surface adherence, resulting SN inhibit EC and stimulate FB proliferation. Serum is required for the expression of FB proliferation.