Inhibition of selectin- and integrin-mediated inflammatory response after burn injury.
Inflammation and microvascular injury in the areas adjacent to burn wounds produces extension of postburn tissue necrosis. Leukocytes are potent mediators of the local inflammatory response preceding tissue necrosis, and the selectin and integrin adhesion molecules have been implicated in leukocyte-mediated tissue destruction. We sought to examine the role of L-selectin (CD62-L) and CD18 in leukocyte accumulation and tissue necrosis following burn injury. New Zealand White rabbits (n = 36) were subjected to burn injury and were randomized to treatment with saline (control) or monoclonal antibodies to L-selectin or CD18. Animals given the anti-L-selectin antibody demonstrated reduced immunohistochemical evidence of leukocyte accumulation at 24 hr postinjury but did not show improved wound perfusion or reduced tissue necrosis. Animals in the anti-CD18 group showed significantly improved tissue survival and improved tissue perfusion but had grades of leukocyte accumulation similar to those in the control group. These observations suggest that leukocyte accumulation is partially L-selectin dependent and that leukocyte accumulation alone is not sufficient to cause changes in blood flow and tissue destruction, both of which appear to be largely CD18 mediated.
Nwariaku
F
F
Department of Surgery, University of Texas Southwestern Medical Center at Dallas 75235-9031, USA.
Sikes
P J
PJ
Lightfoot
E
E
Mileski
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002056:Burns / Q000503:physiopathology*; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control*; D019041:L-Selectin / Q000276:immunology / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D014945:Wound Healing
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D007074:Immunoglobulin G; D019041:L-Selectin