Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation.
The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation. Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation. Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels. High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis. Factor XI levels were decreased only during the acute phase. Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors. Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase. PG-APS failed to activate the contact system in vitro. Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important.
DeLa Cadena
R A
RA
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Laskin
K J
KJ
Pixley
R A
RA
Sartor
R B
RB
Schwab
J H
JH
Back
N
N
Bedi
G S
GS
Fisher
R S
RS
Colman
R W
RW
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D002473:Cell Wall; D005172:Factor XI / Q000032:analysis; D005260:Female; D007249:Inflammation / Q000209:etiology*; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007704:Kininogens / Q000097:blood; D010457:Peptidoglycan / Q000008:administration & dosage; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage; D011288:Prekallikrein / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D013290:Streptococcal Infections / Q000503:physiopathology*; D013297:Streptococcus pyogenes / Q000472:pathogenicity*
D007704:Kininogens; D010457:Peptidoglycan; D011135:Polysaccharides, Bacterial; D000990:Antithrombin III; D005172:Factor XI; D011288:Prekallikrein