Inhibition of collagen synthesis by mononuclear cell supernates.

Mononuclear cell infiltration and alteration in the connective tissues are prominent features of the inflammatory response in a number of diseases. To determine whether mononuclear cell products can modulate collagen synthesis, human peripheral mononuclear cells from normal donors were isolated by Ficoll-Hypaque gradient centrifugation and then incubated for 48 h with or without phytohemagglutinin. Confluent cultures of normal, human skin fibroblasts were incubated with 14Cproline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by 14Chydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of 14Cproline was not significantly affected by addition of the mononuclear cell supernates, but as much as 90% decrease in the synthesis by the fibroblasts of labeled collagen was found relative to controls. Supernates from the phytohemagglutinin-stimulated cultures were more active than those from nonstimulated cells. These results suggest that mononuclear cells can synthesize a factor(s) which can selectively inhibit collagen synthesis.