Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate.
Clodronate liposomes were given to rats via intratracheal inhalation to investigate the importance of alveolar macrophages (AMs) in inhaled endotoxin-induced lung injury. When AM depletion was maximal (87% to 90%), rats were exposed to lipopolysaccharide (LPS) or saline. Neither clodronate nor saline liposomes induced an influx of neutrophils (PMNs) into the lungs. However, depleted LPS-exposed rats had 5- to 8-fold higher numbers of lavage PMNs and greater lavage cell reactive oxygen species release compared to undepleted rats. Although AM depletion by itself did not significantly increase inflammatory cytokine expression in lung tissue, LPS-induced message levels for interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were approximately 2-fold higher in AM-depleted rats compared to undepleted rats. These results indicate that cells other than AMs can recruit inflammatory cells into the lungs during acute LPS-induced injury and that AMs play an important suppressive role in the innate pulmonary inflammatory response.
Elder
A
A
Department of Environmental Medicine, University of Rochester, New York 14642, USA. Alison_Elder@urmc.rochester.edu
Johnston
C
C
Gelein
R
R
Finkelstein
J
J
Wang
Z
Z
Notter
R
R
Oberdörster
G
G
D000280:Administration, Inhalation; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004002:Clodronic Acid / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
D000963:Antimetabolites; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D004002:Clodronic Acid; D012965:Sodium Chloride; D009195:Peroxidase