Selective up-regulation of human alveolar macrophage collagenase production by lipopolysaccharide and comparison to collagenase production by fibroblasts.

Collagenase catalyzes the initial and rate-limiting step in interstitial collagen degradation. Human alveolar macrophages produce both a fibroblast-like procollagenase and tissue inhibitor of metalloproteinases (TIMP). To define the potential of macrophages to express collagenase and TIMP, we have studied the effects of certain cell culture variables and LPS on in vitro production of these proteins. Our data indicate: 1) human macrophages cultured in a 1/1 (v/v) mixture of HAM F-12:DME produce two- to three-fold greater quantities of procollagenase (but not TIMP) as compared to HAM F-12, DME, or alpha-MEM alone; 2) maximal collagenase expression requires the further addition of LPS, whereas TIMP production is optimized by 5% fetal bovine serum alone; 3) the up-regulation of macrophage procollagenase by LPS represents a highly selective biologic response when compared to changes induced in other secreted and intracellular proteins; 4) measurements of steady state procollagenase mRNA by Northern blot analysis suggest that the LPS effect is mediated at a pre-translational level; and finally 5) on a per cell basis, human alveolar macrophages cultured under optional conditions secrete approximately 20% of the collagenase and approximately 10% of the TIMP elaborated by stimulated human fibroblasts. We conclude that procollagenase and TIMP secretion by human alveolar macrophages in vitro is strikingly responsive to variations in cell culture conditions and that an especially noteworthy selective upregulation of procollagenase secretion by LPS is probably modulated by a transcriptional mechanism. The macrophage synthetic potential for procollagenase suggests a potentially important role for these cells in directly mediating collagen turnover.