Monocyte procollagenase and tissue inhibitor of metalloproteinases. Identification, characterization, and regulation of secretion.
Alveolar macrophages have been shown to secrete a procollagenase and the tissue inhibitor of metalloproteinases (TIMP), which are similar or identical to the corresponding proteins of human skin fibroblasts. Little is known, however, about the collagenolytic activity of normal human monocytes. We have applied immunologic, biochemical, and molecular biologic tools to examine the collagenolytic profile of freshly isolated peripheral blood monocytes. Our studies indicate that: 1) monocytes are capable of producing both procollagenase and TIMP that are identical to the corresponding products of skin fibroblasts, alveolar macrophages, and U-937 cells; 2) unstimulated monocytes in vitro secrete high levels of TIMP, but little or no procollagenase; 3) an as yet unidentified component(s) of serum are required for in vitro production of TIMP (but not procollagenase) by monocytes; 4) even when stimulated, monocytes secrete much smaller quantities of procollagenase in comparison with macrophages; and 5) regulation of the secretion of procollagenase and TIMP by monocytes exhibits a high degree of individual variability, but is nevertheless subject to clearly different control mechanisms than our previous findings would indicate for alveolar macrophages. Monocytes thus express a macrophage-like, rather than a neutrophil-like, profile of proteins capable of mediating collagen turnover, the regulation of which is distinct from that of more differentiated alveolar macrophages. Further study of monocyte and macrophage collagenolytic activities may provide insights into both the cell biology of mononuclear phagocyte maturation and the mechanisms by which such cells mediate the turnover of interstitial collagens.
Campbell
E J
EJ
Department of Medicine, Jewish Hospital at Washington University Medical Center, St. Louis, Missouri 63110.
Cury
J D
JD
Lazarus
C J
CJ
Welgus
H G
HG
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017364:Collagenases; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D004792:Enzyme Precursors / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D005779:Immunodiffusion; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D012867:Skin / Q000201:enzymology; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase