title: Role of alveolar epithelial cell intercellular adhesion molecule-1 in host defense against Klebsiella pneumoniae.
abstract: Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I alveolar epithelial cells (AEC) in the normal alveolar space. We postulate that AEC ICAM-1 enhances the antimicrobial activity of macrophages and neutrophils in the alveolar space. Wild-type and mutant mice deficient in ICAM-1 were inoculated intratracheally with Klebsiella pneumoniae. After 10 days, 43% of the ICAM-1 mutant mice had died compared with 14% of the wild-type controls (P = 0.003). Significantly more bacteria were isolated from lungs of ICAM-1 mutant mice than controls 24 h after inoculation (log colony-forming units 5.14 +/- 0.21 vs. 3.46 +/- 0. 16, P = 0.001). However, neutrophil recruitment to the lung was not different. In similar experiments in the rat, inhibition of alveolar ICAM-1 by intratracheal administration of antibody resulted in significantly impaired clearance of K. pneumoniae. The role of phagocyte interactions with AEC ICAM-1 for antimicrobial activity was investigated in vitro using primary cultures of rat AEC that express abundant ICAM-1. Alveolar macrophage phagocytosis and killing of K. pneumoniae were increased significantly in the presence of AEC; these effects were inhibited significantly (47.5 and 52%, respectively) when AEC ICAM-1 was blocked. Similarly, neutrophil phagocytic activity for K. pneumoniae in the presence of AEC in vitro was decreased when ICAM-1 on the AEC surface was blocked. Thus in the absence of ICAM-1, there is impaired ability to clear K. pneumoniae from the lungs, resulting in increased mortality. These studies indicate that AEC ICAM-1 plays an important role in host defense against K. pneumoniae by determining the antimicrobial activity of phagocytes within the lung.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: O'Brien
authors.forename: T J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: K A
authors.initials: KA
authors.lastname: Bucknell
authors.forename: S E
authors.initials: SE
authors.lastname: Wilcoxen
authors.forename: R
authors.initials: R
authors.lastname: Paine
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D015169:Colony Count, Microbial; D004847:Epithelial Cells / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D008168:Lung / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018799:Intercellular Adhesion Molecule-1