title: Shedding of soluble ICAM-1 into the alveolar space in murine models of acute lung injury.
abstract: Intercellular adhesion molecule-1 (ICAM-1; CD54) is an adhesion molecule constitutively expressed in abundance on the cell surface of type I alveolar epithelial cells (AEC) in the normal lung and is a critical participant in pulmonary innate immunity. At many sites, ICAM-1 is shed from the cell surface as a soluble molecule (sICAM-1). Limited information is available regarding the presence, source, or significance of sICAM-1 in the alveolar lining fluid of normal or injured lungs. We found sICAM-1 in the bronchoalveolar lavage (BAL) fluid of normal mice (386 +/- 50 ng/ml). Additionally, sICAM-1 was spontaneously released by murine AEC in primary culture as type II cells spread and assumed characteristics of type I cells. Shedding of sICAM-1 increased significantly at later points in culture (5-7 days) compared with earlier time points (3-5 days). In contrast, treatment of AEC with inflammatory cytokines had limited effect on sICAM-1 shedding. BAL sICAM-1 was evaluated in in vivo models of acute lung injury. In hyperoxic lung injury, a reversible process with a major component of leak across the alveolar wall, BAL fluid sICAM-1 only increased in parallel with increased alveolar protein. However, in lung injury due to FITC, there were increased levels of sICAM-1 in BAL that were independent of changes in BAL total protein concentration. We speculate that after lung injury, changes in sICAM-1 in BAL fluid are associated with progressive injury and may be a reflection of type I cell differentiation during reepithelialization of the injured lung.
authors.affiliation: Pulmonary Section (111G), Veterans Affairs Medical Center, 2215 Fuller Road, Ann Arbor, MI 48105, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mendez
authors.forename: Susan B
authors.initials: SB
authors.lastname: Morris
authors.forename: Steven
authors.initials: S
authors.lastname: Wilcoxen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Greeson
authors.forename: Bethany
authors.initials: B
authors.lastname: Moore
authors.forename: Robert
authors.initials: R
authors.lastname: Paine
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D018496:Hyperoxia; D007132:Immunoglobulin Isotypes / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D007132:Immunoglobulin Isotypes; D018799:Intercellular Adhesion Molecule-1