Phagocytic Release and Activation of Human Leukocyte Procollagenase

• Published in: Nature (London) 1973-12, Vol.246 (5433), p.417-419
• Main Authors: ORONSKY, ARNOLD L, PERPER, ROBERT J, SCHRODER, HENRY C
• Format: Article
• Language: English
• Subjects: Carbon Radioisotopes; Collagen - metabolism; Enzyme Activation - drug effects; Enzyme Precursors - blood; Humanities and Social Sciences; Humans; Immunoglobulin G; In Vitro Techniques; letter; Leukocytes - enzymology; Microbial Collagenase - blood; multidisciplinary; Phagocytosis; Rheumatoid Factor - pharmacology; Science; Science (multidisciplinary); Trypsin - pharmacology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/246417a0

DESTRUCTION of collagen-containing structures occurs in those inflammatory disease states which are characterised by the infiltration of large numbers of granulocytic leukocytes 1 . The degradation of collagen fibrils is probably mediated by a specific mammalian collagenase, since native collagen at physiological p H and temperature is resistant to hydrolysis by other proteolytic enzymes 2 . Active collagenase initially identified in culture fluids of tadpole tail 3 has since been demonstrated in cultures of human skin 4 , gingiva 5 , and rheumatoid synovium 6 . Furthermore, collagenase has been demonstrated in human rheumatoid synovial fluid and extracted directly from human granulocytic leukocytes 7,8 . Recently, an inactive collagenase precursor was extracted from human leukocytes 9 . We now report that a collagenase precursor is liberated in large quantity from viable cells during phagocytosis of aggregated human γ globulin (AHGG). In addition, we show that the neutrophil is the principal source of this proenzyme, with only small amounts present in lymphocytes or lymphoblasts. The proenzyme can be activated by trypsin or rheumatoid synovial fluids but not by osteoarthritic synovial fluid.