Recruitment of peripheral mononuclear cells by mammalian collagenase digests of type I collagen.
Type I collagen is highly susceptible to proteolytic cleavage by neutral mammalian collagenase. Following an initial site specific cleavage of the substrate, two characteristic products are generated, TCA and TCB. These two products then spontaneously denature and are degraded into multiple smaller molecular weight peptides. We prepared TCA and TCB from native type I collagen by the action of rat uterine fibroblast neutral collagenase. In addition we prepared denatured type I alpha chains and exposed them to the action of collagenase under controlled conditions in order to generate small molecular weight peptides. We then examined intact type I collagen, TCA and TCB and type I gelatin peptides for chemotactic activity in a Boyden chamber assay using both human peripheral monocytes and polymorphonuclear leucocytes as target cells. Intact type I collagen, while chemotactic for neutrophils, failed to elicit any chemotactic response in mononuclear cells. In addition, the results demonstrate an absence of any detectable chemotactic activity for either TCA or TCB when human peripheral monocytes were used as the target cells. However, type I collagen peptides demonstrated chemotactic activity for peripheral monocytes. Maximum cell migration was found with digests which had been exposed to neutral mammalian collagenase for three to four hours. No chemotactic activity was found using the same peptides, when neutrophils were used as the target cells. The data strongly suggest that chemotactic activity for mononuclear cells, normally suppressed in intact type I collagen, is revealed and/or activated by neutral collagenase digestion. Conversely, chemotactic activity for neutrophils is lost when intact type I collagen is digested into smaller molecular weight fragments.(ABSTRACT TRUNCATED AT 250 WORDS)
Malone
J D
JD
Department of Medicine, St. Louis University, MO.
Richards
M
M
Jeffrey
J J
JJ
D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003094:Collagen / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D003012:Microbial Collagenase / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology
D002630:Chemotactic Factors; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005780:Gelatin; D003094:Collagen; D003012:Microbial Collagenase