Alterations in collagen production in mixed mononuclear leukocyte-fibroblast cultures.

Abstract

The cell-cell interactions between fibroblasts and mononuclear leukocytes (MNL) which promote alterations in collagen accumulation were examined using a system of coculture of human fibroblasts and peripheral blood MNL. The stimulation of collagen production was optimal after 48 h of coculture, and the increase in collagen correlated directly with the number of MNL added. The enhancement of collagen production was seen in both autologous and allogeneic cocultures. Stimulation of noncollagenous protein was also noted. Coculture supernatants contained soluble substances that were capable of stimulating collagen production, although they stimulated collagen production to a lesser degree than direct coculture. Fractionation of these supernatants on Sephadex G-200 revealed a predominant area of stimulatory activity at 160,000 MW. Lesser areas of activity were noted at MW of 80,000 and 25,000. Determination of the types of collagen produced by fibroblasts during coculture with MNL showed that the ratio of type I:III collagen was decreased. These alterations in both the quantitative and qualitative accumulation of collagen mimic the changes often seen in wound healing and early inflammation, suggesting that cellular interactions between fibroblasts and MNL may be important in the modulation of collagen production in normal and pathologic states.