DEPLETION OF ALVEOLAR MACROPHAGES DECREASES NEUTROPHIL CHEMOTAXIS TO PSEUDOMONAS AIRSPACE INFECTIONS

The mechanism for neutrophil (PMN) influx into infected airspaces of t he lung is not known. To determine whether alveolar macrophage product s are important in the initiation of chemotaxis, we depleted rats of a lveolar macrophages by aerosolizing negatively charged oligolamellar l iposomes complexed to clodronate disodium. Ninety-five percent of the alveolar macrophages were depleted, and lung injury and inflammation w ere minimized with this depletion technique. Rats depleted of alveolar macrophages were then anesthetized, and either 5 x 10(6) colony-formi ng units (CFU) or 5 x 10(7) CFU of Pseudomonas aeruginosa were instill ed into the airspaces of these animals. When recombinant macrophage in flammatory protein MIP-2 was intratracheally instilled into rats deple ted of alveolar macrophages, PMN were recruited to their airspaces. No netheless, PMN numbers were decreased in the lavage fluids when modera te or large inoculums of bacteria were instilled into depleted rats, a lthough the PILIN response appeared dose dependent. Levels of bioactiv e tumor necrosis factor-alpha and immunoreactive proteins CINC/gro (cy tokine-induced PMN chemoattractant) in the lavage fluids obtained from infected rats depleted of alveolar macrophages were significantly dec reased compared with the levels in the lavage fluids obtained from nor mal infected rats. MIP-S mRNA expression, as detected by Northern anal ysis, was also decreased in the infected lungs of depleted rats, and t he lavage fluid from these rats had significantly decreased chemotacti c activity. Therefore these results suggest that alveolar macrophage p roducts play a direct role in the initial recruitment of PMN into infe cted lungs.