Kinetics of C5a release in cardiac lymph of dogs experiencing coronary artery ischemia-reperfusion injury.
Previous studies of myocardial ischemia suggest that complement activation may play a central role in the inflammatory response during reperfusion. Our previous work has demonstrated neutrophil chemotactic activity to be present in reperfusion canine cardiac lymph after myocardial ischemia and infarction. To evaluate the contribution of the complement-dependent anaphylatoxin C5a to this neutrophil chemotactic activity, rabbit antiserum to canine C5a was prepared. At dilutions > 1:500 but < 1:2,000, the antiserum abolished the ability of zymosan-activated dog serum to induce a ruffled, bipolar morphology in isolated neutrophils used as a bioassay of chemotactic stimulation. This antiserum did not affect similar morphological changes in neutrophils exposed to platelet activating factor (10(-7)-10(-6) M) or recombinant human interleukin-8 (10(-9)-10(-8) M); thus, we deemed it functionally specific for canine C5a. In a pattern similar to what we previously reported, cardiac lymph collected before a 1-hour ligation of the left circumflex coronary artery had little ability to alter the morphology of canine neutrophils (shape change index, 11.3 +/- 4.6, mean +/- SEM; n = 7), but by 1 hour of reperfusion, lymph activated neutrophils significantly in five of seven dogs (mean shape change index, 72.6 +/- 17.7; p < 0.01). At 2 hours of reperfusion, neutrophil activation by lymph occurred in six of seven dogs (mean shape change index, 103.1 +/- 22.2). At 3 hours of reperfusion, cardiac lymph of only three of six dogs caused neutrophil activation, and at 4 hours of reperfusion, this activity was evident in lymph from only two of five dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Dreyer
W J
WJ
Department of Pediatrics, Methodist Hospital, Houston, Tex.
Michael
L H
LH
Nguyen
T
T
Smith
C W
CW
Anderson
D C
DC
Entman
M L
ML
Rossen
R D
RD
D000818:Animals; D002630:Chemotactic Factors / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000276:immunology*; D004285:Dogs; D007106:Immune Sera; D007120:Immunochemistry; D016209:Interleukin-8 / Q000494:pharmacology; D008196:Lymph / Q000276:immunology*; D009206:Myocardium / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D015427:Reperfusion Injury / Q000276:immunology*; D013997:Time Factors
D002630:Chemotactic Factors; D007106:Immune Sera; D016209:Interleukin-8; D010972:Platelet Activating Factor; D015936:Complement C5a