Oxidant-mediated, CD18-dependent microvascular dysfunction induced by complement-activated granulocytes.
To determine the mechanisms whereby complement-activated granulocytes induce microvascular dysfunction in skeletal muscle, we examined the effect of antineutrophil serum (ANS), IB4 (a monoclonal antibody that inhibits CD18-dependent neutrophil adherence), xanthine oxidase inhibition or inactivation, deferoxamine, and catalase on the increase in canine gracilis muscle microvascular permeability induced by intravascular administration of zymosan-activated plasma (ZAP). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient (sigma) for total plasma proteins, and the extent of neutrophil infiltration was estimated by assessing muscle myeloperoxidase activity. ZAP infusion was associated with a marked increase in vascular permeability compared with control muscles that received no treatment or to muscles treated with zymosan heat-inactivated plasma (ZIP) (sigma = 0.51 +/- 0.04, 0.89 +/- 0.02, and 0.90 +/- 0.01, respectively). Estimates of sigma in animals rendered neutropenic with ANS, or treated with IB4, deferoxamine, or catalase before ZAP infusion were not significantly different from values obtained in control or ZIP-treated muscles (sigma = 0.96 +/- 0.02, 0.88 +/- 0.03, 0.85 +/- 0.02, and 0.79 +/- 0.01, respectively). However, xanthine oxidase inactivation or inhibition provided no protection from this ZAP-induced microvascular dysfunction (sigma = 0.58 +/- 0.02 and 0.58 +/- 0.01, respectively). In addition, neutropenia and inhibition of neutrophil adherence also prevented ZAP-induced increases in vascular resistance and tissue neutrophil infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)
Carden
D L
DL
Department of Physiology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Smith
J K
JK
Korthuis
R J
RJ
D000818:Animals; D001769:Blood; D018821:CD18 Antigens; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion; D003165:Complement System Proteins / Q000502:physiology*; D003676:Deferoxamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006358:Hot Temperature; D007106:Immune Sera / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000098:blood supply*; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D014655:Vascular Resistance; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D015054:Zymosan / Q000494:pharmacology
D018821:CD18 Antigens; D007106:Immune Sera; D016028:Receptors, Leukocyte-Adhesion; D003165:Complement System Proteins; D015054:Zymosan; D002374:Catalase; D009195:Peroxidase; D014969:Xanthine Oxidase; D003676:Deferoxamine