Blood monocytes attenuate lung fibroblast contraction of three-dimensionalcollagen gels in coculture

Mononuclear phagocytes can interact with mesenchymal cells and extracellula r matrix components that are crucial for connective tissue rearrangement. W e asked whether blood monocytes can alter matrix remodeling mediated by hum an lung fibroblasts cultured in a three-dimensional collagen gel. Blood mon ocytes from healthy donors (>95% pure) were cast into type I collagen gels that contained lung fibroblasts. Monocytes in coculture inhibited the fibro blast-mediated gel contractility in a time- and concentration-dependent man ner. The concentration of PGE(2), a well-known inhibitor of gel contraction , was higher (P < 0.01) in media from coculture; this media attenuated fibr oblast gel contraction, whereas conditioned media from either cell type cul tured alone did not. Three-dimensional cultured monocytes responded to cond itioned media from cocultures by producing interleukin-1 beta and tumor nec rosis factor-alpha, whereas fibroblasts increased synthesis of PGE(2). Anti bodies to interleukin-1 beta and tumor necrosis factor-alpha blocked the mo nocyte inhibitory effect and reduced the amount of PGE(2) produced. The abi lity of monocytes to block the fibroblast contraction of matrix may be an i mportant mechanism in regulating tissue remodeling.