ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space.
Neutrophil recruitment into lung constitutes a major response to airborne endotoxins. In many tissues endothelial intercellular adhesion molecule-1 (ICAM-1) interacts with lymphocyte function associated antigen-1 (LFA-1) on neutrophils, and this interaction plays a critical role in neutrophil recruitment. There are conflicting reports about the role of ICAM-1 in neutrophil recruitment into lungs. We studied neutrophil recruitment into alveolar space in a murine model of aerosolized LPS-induced lung inflammation. LPS induces at least a 100-fold increase in neutrophil numbers in alveolar space, as determined by flow cytometry of bronchoalveolar lavage fluid. Neutrophil recruitment was reduced by 54% in ICAM-1 null mice and by 45% in LFA-1 null mice. In wild-type mice treated with anti-ICAM-1 and anti-LFA-1 antibodies, there was 51 and 58% reduction in the neutrophil recruitment, respectively. In chimeric mice, generated by the transplantation of mixtures of bone marrows from LFA-1 null and wild-type mice, the normalized recruitment of LFA-1 null neutrophils was reduced by 60% compared with wild-type neutrophils. Neither the treatment of ICAM-1 null mice with a function-blocking antibody to LFA-1 nor the treatment of LFA-1 null mice with anti-ICAM-1 antibody resulted in further reduction in the recruitment compared with untreated ICAM-1 null and LFA-1 null mice. We conclude that ICAM-1 and LFA-1 play critical roles in the recruitment of neutrophils into the alveolar space in aerosolized LPS-induced lung inflammation, and LFA-1 serves as a ligand of ICAM-1 in the lung.
Basit
Abdul
A
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, 22908, USA.
Reutershan
Joerg
J
Morris
Margaret A
MA
Solga
Michael
M
Rose
C Edward
CE
Ley
Klaus
K
D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002448:Cell Adhesion / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology*
D000336:Aerosols; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1