title: Effect of ICAM-1 blockade on lung inflammation and physiology during acute viral bronchiolitis in rats.
abstract: 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.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison 53792-3244, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: H
authors.initials: H
authors.lastname: Mehta
authors.forename: M R
authors.initials: MR
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: S L
authors.initials: SL
authors.lastname: Hefle
authors.forename: R F
authors.initials: RF
authors.lastname: Lemanske
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1