Leukocyte Kinetics and Migration in the Lungs

Abstract

Neutrophil recruitment into the alveolar air space is central to the inflammatory response in the lung. Unlike the systemic microcirculation, the pulmonary capillaries but not venules are the primary site of neutrophil recruitment into the inflamed air space. Neutrophils are larger in diameter than most pulmonary capillaries and are required to deform into an elliptical shape prior to entrance into a capillary segment. The time spent during deformation, entrance, and transit through the capillary network results in concentration of neutrophils within the pulmonary microcirculation. This chapter provides an overview of the molecular and biophysical mechanisms that regulate neutrophil margination in the lung microcirculation during homeostasis and recruitment into the air spaces during inflammation. Here, we describe neutrophil recruitment into the inflamed air spaces as a coordination of five sequential steps of capillary sequestration and retention, trans-luminal crawling, trans-endothelial migration, trans-interstitial migration, and trans-epithelial migration. Our current understanding of these five sequential steps is partially based on intravital microscopy studies performed in the nonpulmonary vascular beds of mice. Recently, intravital microscopy approaches that allow visualization of the pulmonary microcirculation in live mice have become available. Intravital microscopy studies of the lung should be conducted in mice to elucidate the molecular pathways that dictate neutrophil kinetics in the lung.