Dermal mast cell granules bind interstitial procollagenase and collagenase.
In order to identify structures in human skin that bind collagenase, sections from frozen or paraffin-embedded skin were incubated with either procollagenase or activated collagenase. After washing, bound procollagenase or collagenase was detected by immunofluorescence microscopy. In normal skin, procollagenase bound only to isolated granular dermal cells that were identified as mast cells on the basis of staining with fluoresceinated avidin and pinacyanol erythrosinate. When mast cells were degranulated by exposure to the ionophore A23187, extracellular granules bound procollagenase. Of various pathologic conditions examined, the highest binding of procollagenase occurred in specimens of urticaria pigmentosa. Procollagenase bound to granular cells and to abundant granules scattered throughout the dermis. Binding could be abolished by pre-treatment of tissue sections with heparinase or by pre-incubation of procollagenase with soluble heparin, suggesting that heparin is the binding agent in the granules. Activated collagenase also bound to dermal mast cells but in addition bound strongly to the dermal collagen. Enzymatic activity of activated collagenase was not inhibited by heparin in concentrations up to 10 mg/ml. There is evidence that mast cell tryptase can contribute to procollagenase activation. This study further supports a role for mast cells in collagenolysis by demonstrating that heparin from mast cells binds procollagenase and possibly serves as a reservoir for procollagenase, which may then subsequently be activated.
Krejci
N C
NC
Department of Dermatology, Stanford University School of Medicine, CA 94305.
Knapp
D M
DM
Rudd
R J
RJ
Bauer
E A
EA
McGuire
J
J
D000818:Animals; D002232:Carbocyanines; D017364:Collagenases; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D004923:Erythrosine / Q000031:analogs & derivatives; D005110:Extracellular Space / Q000201:enzymology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008407:Mast Cells / Q000648:ultrastructure*; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012867:Skin / Q000166:cytology; D013045:Species Specificity; D013194:Staining and Labeling
D002232:Carbocyanines; D004792:Enzyme Precursors; C092665:pinacyanol erythrosinate; D006493:Heparin; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase; D004923:Erythrosine