Depletion of alveolar macrophages decreases neutrophil chemotaxis
to pseudomonas airspace infections.
Hashimoto, Satoru, Jean-Fran[cedilla]cois Pittet, Keelung Hong, Hans
Folkesson, Gregory Bagby, Lester Kobzik, Charles Frevert, Kazuyoshi
Watanabe, Susumu Tsurufuji, Jeanine Wiener-Kronish.
Departments of Anesthesia and Medicine and the Cardiovascular
Research Institute and Cancer Research Institute, University of
California, San Francisco, CA, 94143; Kyoto Prefectural University of
Medicine, Department of Anesthesiology, Kyoto 602, Japan; Department
of Physiology, Lousiana State University Medical Center, New Orleans,
LA 70112; Physiology Program, Harvard School of Public Health,
Boston, MA,02115-6195; Institute of Cytosignal Research, Inc., Tokyo
140, Japan
APStracts 2:0234L, 1995.
The mechanism for neutrophil 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
5x106cfu or 5x 107cfu of Pseudomonas aeruginosa were instilled into
the airspaces of these animals. When recombinant MIP-2 was
intratracheally instilled into rats depleted of alveolar macrophages,
neutrophils were recruited to their airspaces. Nonetheless,
neutrophil numbers were decreased in the lavage fluids when moderate
or large inoculums of bacteria were instilled into depleted rats,
although the neutrophil response appeared dose-dependent. Levels of
bioactive TNF[alpha] and immunoreactive CINC/gro in the lavage fluids
obtained from infected rats depleted of alveolar macrophages were
significantly decreased compared to 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 neutrophils into infected lungs.
Received 12 April 1995; accepted in final form 29 November 1995.
APS Manuscript Number L115-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95