Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat.
A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroArg (P8720), was used to define the relationship between the kallikrein-kinin (K-K) system and acute intestinal inflammation induced by bacterial peptidoglycan-polysaccharide (PG-APS) in Lewis rats. Group I received human serum albumin (HSA) intramurally in the intestine and was treated with HSA. Group II received PG-APS and was treated with P8720. Group III received PG-APS and was treated with HSA. P8720 attenuated the decrease of high-molecular-weight kininogen and factor XI activity (group II vs group III, P < 0.01). P8720 therapy significantly but modestly decreased acute intestinal inflammation measured by gross gut score (P < 0.01) and more dramatically reduced the tissue myeloperoxidase activity (P < 0.05), a measure of granulocyte recruitment, in group II compared with group III. We conclude that the K-K system is directly involved in the pathogenesis of the acute phase of experimental acute inflammation. A specific inhibitor may modulate inflammatory bowel disease.
Stadnicki
A
A
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
DeLa Cadena
R A
RA
Sartor
R B
RB
Bender
D
D
Kettner
C A
CA
Rath
H C
HC
Adam
A
A
Colman
R W
RW
D000208:Acute Disease; D000818:Animals; D001896:Boron Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D016234:Kallikrein-Kinin System / Q000187:drug effects; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009842:Oligopeptides / Q000627:therapeutic use*; D010457:Peptidoglycan; D051381:Rats; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013297:Streptococcus pyogenes
D001896:Boron Compounds; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010457:Peptidoglycan; D012709:Serum Albumin; C099457:benzoyl-prolyl-phenylalanyl-boroarginine; D007610:Kallikreins