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 reten tion of stiffened neutrophils, but L-selectin-mediated leukocyte/endothelia l interaction may be an essential step. We investigated the effect of the a nti-L-selectin antibody HuDreg 200 on leukocyte sequestration and microhemo dynamics in alveolar capillaries in a model of acute endotoxemia. We used i n vivo fluorescence microscopy to analyze kinetics of fluorescently labeled red and white blood cells in alveolar capillary networks of the rabbit lun g. 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 mu g/kg bw lipop olysaccharide (LPS) of Escherichia coil 0111:84, or the combination of HuDr eg 200 and LPS, respectively. infusion of LPS induced leukocyte sequestrati on in alveolar capillaries, which was accompanied by a reduction of alveola r capillary perfusion and functional capillary density. These effects could be completely blocked by pretreatment of animals with HuDreg 200. We concl ude that L-selectin-mediated leukocyte/endothelial interaction is a necessa ry prerequisite for leukocyte sequestration in alveolar capillaries in this model. Impaired alveolar capillary perfusion appeared to result directly f rom capillary leukocyte sequestration.