Effect of neutrophil migration induced by leukotriene B4 on protein permeability in sheep lung.

Although several types of acute lung microvascular injury require active participation of circulating leukocytes (presumably neutrophils), the relationship between neutrophils and microvascular injury and edema is controversial. We attempted to answer the question, Does neutrophil migration in response to a chemical signal alter endothelial permeability? If so, is this to be regarded as a significant control mechanism for microvascular protein permeability? Because of our interest in pulmonary injury, we attempted to induce neutrophil chemotaxis into the lungs of anesthetized sheep by using leukotriene B4 (LTB4) (2 nmol/ml, 50 ml total) placed in the alveoli of one caudal lung lobe through a fiberoptic bronchoscope. Measurements of pulmonary hemodynamics, lymph dynamics, and alveolar liquid dynamics were made. Compared to chemotaxis into skin, neutrophil migration into alveoli was slow. LTB4 caused a small increase in lung lymph and protein flow, which was slightly more than that in saline controls. Likewise, excess plasma protein entering the alveolar liquid was slightly increased over saline controls. Both results indicate a small increase in liquid and protein flow across the endothelial and alveolar epithelial barriers in response either to the LTB4 or to the neutrophil chemotaxis. Using a worst case analysis, the slight increase in liquid and protein flow across the endothelium and epithelium may be related to quantal leakage of plasma during neutrophil transit, but there is no evidence for any persistent change in microvascular or epithelial permeability.