Role of serine esterases in mast cell activation.
1. A variety of chymotryptic substrates and inhibitors prevented the release of histamine and prostaglandin D2 from rat peritoneal mast cells stimulated with anti-IgE but not the calcium ionophore A23187 or a variety of polyamines. 2. The activity of the compounds was strikingly increased in cells reversibly permeabilized with ATP, indicating the importance of their effective incorporation into the cytosol. 3. The compounds produced a comparable inhibition of immunological, but not pharmacological, histamine release from human mast cells and basophils. 4. Treatment of rat mast cells with anti-IgE led to a marked increase in the total chymotryptic activity expressed by the cells. 5. Immunological, but not pharmacological, stimulation of permeabilized rat mast cells loaded with a fluorescent chymotryptic substrate led to a pronounced and rapid increase in fluorescence, indicating activation of the enzyme and hydrolysis of the substrate. These changes were attenuated by chymotryptic inhibitors. 6. In total, these data provide compelling evidence for the direct involvement of a serine protease in IgE-mediated histamine release from mast cells.
Khiav
B E
BE
Department of Chemistry, University College London.
Pearce
F L
FL
D000818:Animals; D002918:Chymotrypsin / Q000378:metabolism; D004950:Esterases / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006868:Hydrolysis; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014361:Trypsin Inhibitors / Q000494:pharmacology
D005456:Fluorescent Dyes; D018836:Inflammation Mediators; D014361:Trypsin Inhibitors; D004950:Esterases; C022635:serine esterase; D002918:Chymotrypsin