Breakdown of noncollagenous chondromucoprotein matrix by leukocyte lysosome granule lysates from guinea pig, rabbit, and human

Louis J. Ignarro, Arnold L. Oronsky, Robert J. Perper

Research output: Contribution to journalArticle

Abstract

Degradation of the noncollagenous protein-mucopolysaccharide matrix of rabbit ear cartilage in vitro by various enzyme preparations is reported. Cartilage matrix degradation was quantitated by measuring the release of soluble, 35S-labeled, anionic material from cartilage that was previously labeled in vivo with Na2 35SO4. The release of 35S was specific for chondromucoprotein degradation, as evidenced by the parallel release of mucopolysaccharide split products, precipitation of 35S with cetyltrimethyl ammonium bromide and enzyme specificity. Autolytic breakdown of chondromucoprotein proceeded predominantly at pH 5.0 and to a very limited extent at pH 7.4 during an 18-hr incubation at 37°C. Trypsin, chymotrypsin, and elastase provoked chondromucoprotein degradation at pH 7.4, whereas hyaluronidase was more active at pH 5.0. Purified bacterial collagenase did not promote significant breakdown of the noncollagenous portion of cartilate matrix at neutral or acid pH. Lysosome granule lysates of guinea pig and rabbit peritoneal polymor-phonuclear leukocytes were capable of degrading the chondromucoprotein of cartilage matrix at pH 5.0 but not at pH 7.4. Conversely, lysates of granules from human leukocytes damaged cartilage matrix at pH 7.4 but not at pH 5.0. Gold sodium thiomalate (10-4 M) and human serum (10%) inhibited the degradation of guinea pig, matrix provoked by autolysis and by the leukocyte granuleslysates of guinea pig, rabbit and human. The demonstration in human leukocyte granules of neutral protease(s) that damage the noncollagenous chondromucoprotein matrix of cartilage and the finding that gold, an antirheumatic drug, inhibits this deleterious effect, may have a significant bearing on the pathology of connective tissue disease.

Original languageEnglish (US)
Pages (from-to)36-51
Number of pages16
JournalClinical Immunology and Immunopathology
Volume2
Issue number1
DOIs
Publication statusPublished - 1973
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

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