title: The role of leukocytes during acute phase inflammation in crystalline silica-induced lung injury.
abstract: Silicosis is characterized by progressive granulomatous and fibrogenic response in the lung. Inhaled crystalline silica (Qt) induces activation of pulmonary macrophages and leukocyte infiltration in the lung of Qt-treated animals. We investigated the role of leukocyte infiltration and L-selectin during the acute phase of inflammation in developing chronic lung injury in Qt-treated rats. Seventy Wistar male rats were treated with a single transtracheal instillation of Qt (25 mg/kg). Rats were treated intraperitoneally with anti L-selectin monoclonal antibody (mAb), F(ab')2 HRL-3 (HRL-3, a blocking mAb), or RF(ab')2 HRL-2 (HRL-2, a non-blocking mAb)for 4 days before and after Qt injection. Administration of HRL-3 reduced approximately 50% of leukocyte infiltration in the BAL, whereas HRL-2 treatment prior to Qt stimulation showed time-dependent increase of BAL leukocytes. CINC and GRO levels as well as peripheral blood cell counts were similar in HRL-2- or HRL-3-treated animals in the first 4 days of the study. Three months after Qt treatment, extensive granuloma-containing macrophages and leukocytes developed in the lung of the HRL-3-treated rats as compared with the HRL-2-treated rats. Ratio of CD4+ to CD8+ T cells in granulomas did not differ between the HRL-3 and HRL-2 groups. Results suggest that an early phase of leukocyte activation was diminished by blocking L-selectin with the antibody, but treatment with anti-L-selectin increased the formation of granulomas in the Qt-treated rats.
authors.affiliation: Department of Hygiene and Public Health I, School of Medicine, Tokyo Women's Medical University, Japan. ishihara@research.twmu.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Ishihara
authors.forename: T
authors.initials: T
authors.lastname: Yasuhara
authors.forename: S
authors.initials: S
authors.lastname: Ishiyama
authors.forename: H
authors.initials: H
authors.lastname: Kawashima
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000302:isolation & purification / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006099:Granuloma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007442:Intubation, Intratracheal; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D019041:L-Selectin; D012822:Silicon Dioxide