title: Preventing the infiltration of leukocytes by monoclonal antibody blocks the development of progressive ischemia in rat burns.
abstract: Tissue loss as a consequence of thermal trauma occurs in two stages. There is immediate necrosis in tissues directly killed by the thermal energy, followed by a delayed secondary necrosis in neighboring tissues. The infiltration of neutrophils into traumatized tissues is a hallmark of the inflammatory response. Neutrophils have the machinery to kill invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration requires their adherence to the vascular endothelial cell surface. Masking these adhesion sites on neutrophils will block the adhesion of neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to guinea pig leukocyte adhesion sites CD11b/ CD18, and this mAb cross-reacts with rat leukocytes, blocking their adherence. Rats received a "comb burn" composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individual burns convert into a single large wound because the blood flow to the interspaces was terminated, blood vessels were occluded, and leukocytes were present in the extravascular space. The systemic administration of the mAb (50 to 150 microliters) immediately following a comb burn promoted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent vessels by latex vascular casts, blocked extravascular migration of neutrophils histologically at 2 hours, and limited the tissue loss to the original four burns.
authors.affiliation: Wound Healing Laboratory, Shriners Burns Institute, Boston, Mass., USA.
authors.forename: M
authors.initials: M
authors.lastname: Choi
authors.forename: H
authors.initials: H
authors.lastname: Rabb
authors.forename: M A
authors.initials: MA
authors.lastname: Arnaout
authors.forename: H P
authors.initials: HP
authors.lastname: Ehrlich
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002056:Burns / Q000150:complications* / Q000473:pathology; D018821:CD18 Antigens / Q000032:analysis; D002465:Cell Movement; D006168:Guinea Pigs; D007511:Ischemia / Q000209:etiology / Q000517:prevention & control*; D007962:Leukocytes / Q000276:immunology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen