Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation.
Intercellular adhesion molecule-1 (ICAM-1) is known to play a central role in lung inflammation. Limited information, however, is available regarding the expression and biological function of ICAM-1 in the alveolar epithelial compartment. The current report analyses the expression pattern of ICAM-1 in primary cultures of rat alveolar epithelial cells (AECs) and in the rat lung following instillation of bacterial endotoxin (lipopolysaccharide (LPS)) in order to better define the role of alveolar epithelial ICAM-1. AECs stimulated in vitro with LPS were evaluated for ICAM-1 and ICAM-1 messenger ribonucleic acid content. Adherence assays with neutrophils and macrophages were performed. Endotoxin-induced ICAM-1 upregulation on AECs was demonstrated in vivo by immunofluorescence staining. In addition, the effect of intratracheally-instilled anti-ICAM-1 was assessed. Significant upregulation of ICAM-1 occurred in vitro and in vivo on AECs after LPS stimulation. Adherence assays showed a 114% increase in adhesion of neutrophils to AECs. Antibody directed against ICAM-1 reduced this adhesion by 40%. A significant reduction in the number of neutrophils in bronchoalveolar lavage fluid and whole lung was seen under airway ICAM-1 blockade. These data indicate that intercellular adhesion molecule-1 participates in the inflammatory response to lipopolysaccharide-induced lung injury in the distal airways by interacting mainly with neutrophils.
Institute of Anaesthesiology, University of Zurich Medical School, Switzerland. bbeck@physiol.unizh.ch
B
B
Beck-Schimmer
C
C
Madjdpour
S
S
Kneller
U
U
Ziegler
T
T
Pasch
R P
RP
Wüthrich
P A
PA
Ward
R C
RC
Schimmer
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000906:Antibodies; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1