Reduction of burn injury by inhibiting CD18-mediated leukocyte adherence in rabbits.
The progressive nature of dermal ischemia and subsequent tissue destruction within the "zone of stasis" is a central focus in burn research. To examine the role of neutrophils and neutrophil adherence within the zone of stasis, we utilized the monoclonal antibody (MAb) 60.3, directed to the human leukocyte adherence glycoprotein CD18 to block neutrophil adherence to endothelium and intravascular aggregation in a rabbit model of partial-thickness burn. Burns were created by applying an 80 degrees C brass template to the dorsal rabbit skin for 5 or 10 seconds. Animals treated with MAb 60.3 thirty minutes following a 5-second burn had less edema, thinner eschar, and earlier elevation of the eschar than control animals. Histologic analysis revealed an eightfold increase in live hair follicles (p < 0.05) and 43 percent greater reepithelialization at 8 days (p < 0.05) and a 15 percent reduction in burn surface area at 24 hours (p < 0.0001) in the antibody-treated group. There was no significant difference between treatment and control groups exposed to 10-second burns. We conclude that neutrophils and increased neutrophil adherence play important roles in the progressive tissue destruction within the zone of stasis in burns. Furthermore, moderate burn injury may be significantly attenuated by blocking neutrophil adherence functions with a CD18 MAb.
Bucky
L P
LP
Division of Plastic Surgery, Harvard Medical School, Boston, Mass.
Vedder
N B
NB
Hong
H Z
HZ
Ehrlich
H P
HP
Winn
R K
RK
Harlan
J M
JM
May
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D002056:Burns / Q000473:pathology* / Q000503:physiopathology; D018821:CD18 Antigens; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000473:pathology; D006197:Hair / Q000473:pathology; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000473:pathology; D014945:Wound Healing / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion