Effect of ICAM-1 blockade on lung inflammation and physiology during acute viral bronchiolitis in rats.
Viral respiratory infections cause acute bronchiolitis and physiologic dysfunction in human infants and in animals. It is possible that the pulmonary dysfunction is a consequence of the inflammatory cells that are recruited during viral illness. We hypothesized that blockade of intercellular adhesion molecule-1 (ICAM-1), a major cell adhesion molecule, would impede the ingress of leukocytes during viral infection and attenuate virus-induced pulmonary dysfunction. Adult male rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with blocking or nonblocking MAb specific for rat ICAM-1. Respiratory system resistance, oxygenation (PaO2), methacholine responsiveness, and bronchoalveolar lavage (BAL) leukocyte counts were measured in anesthetized, paralyzed, ventilated rats. Treatment with the blocking ICAM-1 antibody reduced virus-induced increases in BAL neutrophils and lymphocytes by 70% (p < 0.001), but did not affect BAL monocytes/macrophages. Peripheral blood leukocyte counts were elevated in anti-ICAM-1 blocking antibody-treated rats (p = 0.0003). Although virus-induced increases in resistance and decreases in PaO2 were not affected by anti-ICAM-1 treatment, there was a small but significant attenuation of virus-induced methacholine hyperresponsiveness (p = 0.02). We conclude that ICAM-1 has an important role in neutrophil and lymphocyte infiltration during respiratory viral illness, and that virus-induced changes in pulmonary physiology are not related directly to the numbers of neutrophils and lymphocytes that migrate to the air spaces during infection.
Sorkness
R L
RL
Department of Medicine, University of Wisconsin, Madison 53792-3244, USA.
Mehta
H
H
Kaplan
M R
MR
Miyasaka
M
M
Hefle
S L
SL
Lemanske
R F
RF
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001990:Bronchiolitis, Viral / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018108:Respirovirus / Q000302:isolation & purification*; D010253:Respirovirus Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1