Human C1 esterase inhibitor attenuates murine mesenteric ischemia/reperfusion induced local organ injury.
BACKGROUND
Complement activation contributes to ischemia and reperfusion (IR)-initiated organ injury. C1 inhibitor (C1 Inh) inhibits the earliest steps of the classical and the mannose binding lectin pathways.


METHODS
To determine whether C1 Inh prevented tissue injury, we performed intestinal IR experiments in BALB/c and C57BL/6 mice.


RESULTS
We found that C1 Inh limits mucosal injury in the two strains in a dose dependent manner. Tissue damage was associated with the accumulation of functional polymorphonuclear cells, which was reduced following C1 Inh treatment. Constitutive nitric oxide synthase activity correlated with the development of injury in the C57BL/6 but not in the BALB/c mouse.


CONCLUSIONS
These findings emphasize the importance of complement activation in ischemia/reperfusion and highlight the potential therapeutic use of C1 Inh in limiting or preventing damage caused by IR.
Karpel-Massler
Georg
G
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
Fleming
Sherry D
SD
Kirschfink
Michael
M
Tsokos
George C
GC
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003176:Complement C3 / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000201:enzymology; D009504:Neutrophils / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013152:Splanchnic Circulation
D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D015777:Eicosanoids; D009195:Peroxidase; D019001:Nitric Oxide Synthase