Pulmonary resident neutrophils regulate the production of GM-CSF and alveolar macrophages

Abstract

Alveolar macrophages exist in the lung airspaces, and their differentiation and function are considerably regulated by the microenvironment. In this study, we examine the important role of resident neutrophil/IL-23/granulocyte/macrophage colony-stimulating factor (GM-CSF) axis in the development and preferential phenotype of alveolar macrophages under physiological conditions. Using CD18-deficient (CD18-/-) mice, we show a correlation between increased granulopoiesis and enhanced alveolar macrophage development in an IL-23- and GM-CSF-dependent manner. The apoptotic neutrophils could inhibit the secretion of IL-23 from alveolar macrophages, which is important for the production of GM-CSF, and depletion of neutrophils disrupted the regulation of IL-23 and GM-CSF. This study reveals a mechanism for the regulation of the local alveolar macrophage population and function by neutrophil apoptosis in the circulatory system. Neutrophils migrate out of circulation and into alveolar space, in which step CD18 is required. The neutrophil apoptosis could inhibit the production of IL-23 by alveolar macrophages, which reduces the level of GM-CSF and thereby regulates the homeostasis and function of alveolar macrophages. This study builds a potential regulatory connection between the circulating leukocytes and the local alveolar macrophage.