Upregulation of Mac-1 surface expression on neutrophils during simulated extracorporeal circulation.
The leukocyte integrin Mac-1 (alpha m beta 2, CD11b/18 CR3, MO1), in addition to binding iC3b, has been shown to be the receptor for the coagulation proteins fibrinogen, factor X, and high molecular weight kininogen. Mac-1 is known to be upregulated by agonists that stimulate neutrophils or monocytes. Previous studies from this laboratory have documented neutrophil activation during cardiopulmonary bypass. We therefore used an experimental model for cardiopulmonary bypass, a simulated extracorporeal circulation, to study the surface expression of Mac-1 on peripheral blood leukocytes by immunofluorescence flow cytometry. The number of Mac-1 receptors in polymorphonuclear leukocytes had increased 2.2 times and 2.9 times baseline by 2 hours at 37 degrees C and 28 degrees C, respectively (p < 0.001). Neutrophil elastase-alpha 1-proteinase inhibitor complexes (a measure of neutrophil degranulation) increased more than sixfold from 41 micrograms/L to 256 micrograms/L after 2 hours at 28 degrees C. The number of Mac-1 receptors expressed on polymorphonuclear leukocytes correlated with polymorphonuclear leukocyte elastase complexes (r = 0.93). Mac-1--bearing lymphocytes did not display any change in receptor number in the simulated extracorporeal circulation. By 2 hours, monocytes at 37 degrees C showed only insignificant increase; at 28 degrees C they displayed a 1.6 times increase (p < 0.05). By maintaining a temperature-matched standing control samples, we could prove that, unlike the Mac-1 in polymorphonuclear leukocytes, this increase in monocyte Mac-1 is not from bypass but is rather an effect of temperature. These data suggest that a receptor for procoagulant proteins on circulating polymorphonuclear leukocytes (Mac-1) is upregulated during simulated extracorporeal circulation.
Kappelmayer
J
J
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140.
Bernabei
A
A
Gikakis
N
N
Edmunds
L H
LH
Colman
R W
RW
D000328:Adult; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002469:Cell Separation; D005112:Extracorporeal Circulation; D005434:Flow Cytometry; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism
D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010196:Pancreatic Elastase