CHEMOTACTIC AND MITOGENIC COMPONENTS OF THE ALVEOLAR MACROPHAGE RESPONSE TO PARTICLES AND NEUTROPHIL CHEMOATTRACTANT

Abstract

The pulmonary response to instilled particulates involves initial efflux of polymorphonuclear leukocytes (PMN) and increased production of alveolar macrophages (AM). The relationships of the cell migration and division components of the AM production to the initial PMN response after intrapulmonary carbon or latex administration were examined. Supernatants of lung lavage taken during early PMN migration to the alveoli promoted sequential migration of PMN, migration of monocytes and division of pulmonary interstitial cells in normal mice. Supernatants taken during the phase of increased cell division in the lung produced no such effects, implying that factors responsible for chemotaxis and mitosis were generated rapidly and were short-lived. A possible source was the interaction of AM with particles, since supernatants of such incubations induced an inflammatory response in vivo. When a synthetic chemoattractant was used, efflux of PMN was followed by macrophages arising from migration of monocytes and division of interstitial cells. Particulate instillation in the lung stimulated a standard inflammatory response in which rapid generation of a factor(s) chemotactic for PMN also attracted mononuclear cells to the alveoli. The initial efflux of cells was explained by migration from the blood, but continued demand or replacement required mitotic activity of precursors. For the alveolar macrophages, this included division of cells in the pulmonary interstitium.