Depletion of alveolar macrophages decreases neutrophil chemotaxis to Pseudomonas airspace infections

Academic Article

Abstract

  • The mechanism for neutrophil (PMN) influx into infected airspaces of the lung is not known. To determine whether alveolar macrophage products are important in the initiation of chemotaxis, we depleted rats of alveolar macrophages by aerosolizing negatively charged oligolamellar liposomes complexed to clodronate disodium. Ninety-five percent of the alveolar macrophages were depleted, and lung injury and inflammation were minimized with this depletion technique. Rats depleted of alveolar macrophages were then anesthetized, and either 5 x 106 colony-forming units (CFU) or 5 x 107 CFU of Pseudomonas aeruginosa were instilled into the airspaces of these animals. When recombinant macrophage inflammatory protein MIP-2 was intratracheally instilled into rats depleted of alveolar macrophages, PMN were recruited to their airspaces. Nonetheless, PMN numbers were decreased in the lavage fluids when moderate or large inoculums of bacteria were instilled into depleted rats, although the PMN response appeared dose dependent. Levels of bioactive tumor necrosis factor-α and immunoreactive proteins CINC/gro (cytokine-induced PMN chemoattractant) in the lavage fluids obtained from infected rats depleted of alveolar macrophages were significantly decreased compared with the levels in the lavage fluids obtained from normal infected rats. MIP-2 mRNA expression, as detected by Northern analysis, was also decreased in the infected lungs of depleted rats, and the lavage fluid from these rats had significantly decreased chemotactic activity. Therefore these results suggest that alveolar macrophage products play a direct role in the initial recruitment of PMN into infected lungs.
  • Digital Object Identifier (doi)

    Author List

  • Hashimoto S; Pittet JF; Hong K; Folkesson H; Bagby G; Kobzik L; Frevert C; Watanabe K; Tsurufuji S; Wiener-Kronish J
  • Volume

  • 270
  • Issue

  • 5 14-5