Histamine-releasing reaction induced by the N-terminal domain of Vibrio vulnificus metalloprotease.
A zinc metalloprotease secreted by Vibrio vulnificus, an opportunistic human pathogen causing septicemia and wound infection, stimulates exocytotic histamine release from rat mast cells. This protease consists of two functional domains: the N-terminal domain that catalyzes proteolytic reaction and the C-terminal domain that promotes the association with a protein substrate or cell membrane. Like the intact protease, the N-terminal domain alone also induced histamine release from rat peritoneal mast cells in a dose- and time-dependent manner. However, the reaction induced was apparently weak and went on more slowly. The nickel-substituted protease or its N-terminal domain, each of which has the reduced proteolytic activity due to decreased affinity to a substrate, showed much less histamine-releasing activity. When injected into the rat dorsal skin, the N-terminal domain also evoked enhancement of the hypodermic vascular permeability, while the activity was comparable to that of the protease. Taken together, the protease may stimulate histamine release through the action of the catalytic center of the N-terminal domain on the target substance(s) on the mast cell membrane. The C-terminal domain may support the in vitro action of the N-terminal domain by coordination of the association of the protease with the membrane, but it may not modulate the in vivo action.
Miyoshi
Shin-ichi
S
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Okayama 700-8530, Japan. miyoshi@pharm.okayama-u.ac.jp
Kawata
Koji
K
Hosokawa
Masayoshi
M
Tomochika
Ken-ichi
K
Shinoda
Sumio
S
D000818:Animals; D001426:Bacterial Proteins; D020134:Catalytic Domain; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments; D010537:Peritoneum / Q000166:cytology; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D041261:Vibrio vulnificus / Q000201:enzymology*
D001426:Bacterial Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C070101:vvP protein, Vibrio vulnificus