Role of complement regulatory membrane proteins in ischaemia-reperfusion injury of rat gastric mucosa.
BACKGROUND
The role of complement in ischaemia-reperfusion injury has not been well investigated. 5I2 is a monoclonal antibody (mAb) directed against a rat membrane inhibitor of the C3 convertase step, which is the rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits the formation of membrane attack complexes.


METHODS
We visualized the tissue distribution of these membrane inhibitors in rat gastrointestinal tract by immunohistochemical staining with the appropriate mAb. Then, we tested the hypothesis that complement regulatory proteins protect rat gastric mucosa against ischaemia-reperfusion stress by using these mAbs. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51Cr]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion.


RESULTS
Rat 6D1 and 5I2 antigens were both widely distributed and predominantly expressed on smooth muscle and endothelial cells in gastrointestinal tracts. Blockade of complement regulatory proteins with 5I2 and 6D1 mAbs resulted in a significant increase in [51Cr]-EDTA clearance after reperfusion.


CONCLUSIONS
These findings support the hypothesis that endogenous complement regulatory proteins may act as important protective factors against ischaemia-reperfusion stress in rat gastric mucosa.
Iwata
F
F
Department of Internal Medicine, West Japan NTT Tokai Hospital, Nagoya, Japan. iwata-f@aichi.med.or.jp
Joh
T
T
Tada
T
T
Okada
N
N
Morgan
B P
BP
Yokoyama
Y
Y
Itoh
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018957:CD59 Antigens / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D002860:Chromium Radioisotopes; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004492:Edetic Acid / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D018957:CD59 Antigens; D002860:Chromium Radioisotopes; D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D003165:Complement System Proteins; D004492:Edetic Acid; D050577:Complement C3-C5 Convertases