Role of anti-L-selectin antibody in burn and smoke inhalation injury in sheep.
We hypothesized that the antibody neutralization of L-selectin would decrease the pulmonary abnormalities characteristic of burn and smoke inhalation injury. Three groups of sheep (n = 18) were prepared and randomized: the LAM-(1-3) group (n = 6) was injected intravenously with 1 mg/kg of leukocyte adhesion molecule (LAM)-(1-3) (mouse monoclonal antibody against L-selectin) 1 h after the injury, the control group (n = 6) was not injured or treated, and the nontreatment group (n = 6) was injured but not treated. All animals were mechanically ventilated during the 48-h experimental period. The ratio of arterial PO2 to inspired O2 fraction decreased in the LAM-(1-3) and nontreatment groups. Lung lymph flow and pulmonary microvascular permeability were elevated after injury. This elevation was significantly reduced when LAM-(1-3) was administered 1 h after injury. Nitrate/nitrite (NO(x)) amounts in plasma and lung lymph increased significantly after the combined injury. These changes were attenuated by posttreatment with LAM-(1-3). These results suggest that the changes in pulmonary transvascular fluid flux result from injury of lung endothelium by polymorphonuclear leukocytes. In conclusion, posttreatment with the antibody for L-selectin improved lung lymph flow and permeability index. L-selectin appears to be principally involved in the increased pulmonary transvascular fluid flux observed with burn/smoke insult. L-selectin may be a useful target in the treatment of acute lung injury after burn and smoke inhalation.
Katahira
Jiro
J
Department of Anesthesiology, The University of Texas Medical Branch, Texas 77555-0833, USA.
Murakami
Kazunori
K
Schmalstieg
Frank C
FC
Cox
Robert
R
Hawkins
Hal
H
Traber
Lillian D
LD
Traber
Daniel L
DL
D000818:Animals; D000906:Antibodies / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure; D002056:Burns / Q000097:blood / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology* / Q000494:pharmacology* / Q000502:physiology; D008196:Lymph / Q000502:physiology; D009500:Neutralization Tests; D009566:Nitrates / Q000097:blood; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000097:blood / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D009566:Nitrates; D019041:L-Selectin