Role of L-selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia.
After a variety of pathophysiologic stimuli, neutrophils accumulate in lung capillaries and contribute to the pathogenesis of acute lung injury. Lung neutrophil sequestration has previously been attributed to mechanical retention of stiffened neutrophils, but L-selectin-mediated leukocyte/endothelial interaction may be an essential step. We investigated the effect of the anti-L-selectin antibody HuDreg 200 on leukocyte sequestration and microhemodynamics in alveolar capillaries in a model of acute endotoxemia. We used in vivo fluorescence microscopy to analyze kinetics of fluorescently labeled red and white blood cells in alveolar capillary networks of the rabbit lung. Investigations were performed over 2 h after an intravenous infusion of 0.2 ml/kg body weight (bw) NaCl, 2 mg/kg bw HuDreg 200, 20 microg/kg bw lipopolysaccharide (LPS) of Escherichia coli 0111:B4, or the combination of HuDreg 200 and LPS, respectively. Infusion of LPS induced leukocyte sequestration in alveolar capillaries, which was accompanied by a reduction of alveolar capillary perfusion and functional capillary density. These effects could be completely blocked by pretreatment of animals with HuDreg 200. We conclude that L-selectin-mediated leukocyte/endothelial interaction is a necessary prerequisite for leukocyte sequestration in alveolar capillaries in this model. Impaired alveolar capillary perfusion appeared to result directly from capillary leukocyte sequestration.
Kuebler
W M
WM
Institute for Surgical Research and Department of Anesthesiology, University of Munich, Germany.
Borges
J
J
Sckell
A
A
Kuhnle
G E
GE
Bergh
K
K
Messmer
K
K
Goetz
A E
AE
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002196:Capillaries / Q000473:pathology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004926:Escherichia coli; D005434:Flow Cytometry; D006439:Hemodynamics / Q000187:drug effects; D019041:L-Selectin / Q000276:immunology / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000098:blood supply* / Q000201:enzymology; D008297:Male; D008856:Microscopy, Fluorescence; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D019041:L-Selectin; D009195:Peroxidase