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 [14C]proline and various amounts of dialyzed supernates from the mononuclear cell cultures. Labeled, newly synthesized collagen was estimated by [14C]hydroxyproline analysis, collagenase digestion, and chromatography on Agarose A-5m in sodium dodecyl sulfate. The total incorporation of [14C]proline 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.
D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003470:Culture Media; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008214:Lymphocytes / Q000502:physiology*; D003012:Microbial Collagenase / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D014176:Protein Biosynthesis
D003470:Culture Media; D003094:Collagen; D003012:Microbial Collagenase; D001205:Ascorbic Acid