Inhibition of leukocyte-endothelial adherence following thermal injury.
Progressive microvascular damage in the tissue adjacent to a cutaneous burn injury results in extension of burn size. The role of neutrophils (PMNs) in the pathogenesis of microvascular injury was investigated by inhibition of PMN adherence to the microvascular endothelium using monoclonal antibodies directed to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using New Zealand White rabbits. Under general anesthesia two sets of three full-thickness burns separated by two 5 x 30-mm zones were produced by applying brass probes heated to 100 degrees C to the animals' backs for 30 sec. Cutaneous blood flow determinations were obtained for 72 hr. Blood flow measurements were performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ). There were five experimental groups; controls given saline alone, n = 12; animals given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n = 6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in the marginal "zone of stasis" between burn contact sites was significantly higher in the antibody-treated animals and administration of the antibodies 30 min after injury was as effective as preburn administration in preserving blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9031.
W
W
Mileski
D
D
Borgstrom
E
E
Lightfoot
R
R
Rothlein
R
R
Faanes
P
P
Lipsky
C
C
Baxter
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D018821:CD18 Antigens; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D007511:Ischemia / Q000473:pathology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion