title: ICAM-1 facilitates alveolar macrophage phagocytic activity through effects on migration over the AEC surface.
abstract: We postulate that intercellular adhesion molecule-1 (ICAM-1) on type I alveolar epithelial cells (AEC) facilitates phagocytic activity of alveolar macrophages (AM) in the alveolus. When wild-type and ICAM-1-deficient mice were inoculated intratracheally with FITC-labeled microspheres, AM phagocytosis of beads (after 1 and 4 h) was significantly reduced in ICAM-1-/- mice compared with controls. To focus on ICAM-1-mediated interactions specifically involving AM and AEC, rat AM were placed in culture with rat AEC treated with neutralizing anti-ICAM-1 F(ab')(2) fragments. Blocking ICAM-1 significantly decreased the AM phagocytosis of beads. Planar chemotaxis of AM over the surface of AEC was also significantly impaired by neutralization of AEC ICAM-1. ICAM-1 in rat AEC is associated with the actin cytoskeleton. Planar chemotaxis of AM was also significantly reduced by pretreatment of the AEC monolayer with cytochalasin B to disrupt the actin cytoskeleton. These studies indicate that ICAM-1 on the AEC surface promotes mobility of AM in the alveolus and is critically important for the efficient phagocytosis of particulates by AM.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Veterans Affairs Medical Center, University of Michigan, Ann Arbor, Michigan 48105, USA. rpaine@umich.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Paine
authors.forename: Susan B
authors.initials: SB
authors.lastname: Morris
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Carlos E O
authors.initials: CE
authors.lastname: Baleeiro
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wilcoxen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D007840:Latex; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008863:Microspheres; D010587:Phagocytosis / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D003432:Cross-Linking Reagents; D007140:Immunoglobulin Fab Fragments; D007840:Latex; D018799:Intercellular Adhesion Molecule-1