THE ROLE OF LEUKOCYTES DURING ACUTE PHASE INFLAMMATION IN CRYSTALLINE SILICA-INDUCED LUNG INJURY

• Published in: Experimental lung research Vol. 27; no. 7; pp. 589 - 603
• Main Author: Ishihara, Tadashi Yasuhara, Shigeru Ishiyama, Hiroto Kawashima, Masayuki Miyasaka, Takayoshi Miyazaki, Yoko
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Informa UK Ltd 2001; Taylor & Francis
• Subjects: Adhesion Molecule Crystalline Silica Leukocytes Pulmonary Granuloma L-SELECTIN; Animals; Antibodies, Blocking - isolation & purification; Antibodies, Blocking - pharmacology; Antibodies, Monoclonal - isolation & purification; Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Chemical and industrial products toxicology. Toxic occupational diseases; Chemotaxis, Leukocyte - physiology; Granuloma - chemically induced; Granuloma - immunology; Granuloma - pathology; Immunoenzyme Techniques; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); Intubation, Intratracheal; L-Selectin - metabolism; Leukocytes - immunology; Lung - drug effects; Male; Medical sciences; Rats; Rats, Wistar; Silicon Dioxide - toxicity; Silicosis - etiology; Silicosis - immunology; Silicosis - pathology; Toxicology; Lung disease; Occupational disease; Pneumoconiosis; Rat; Respiratory disease; Leukocyte; Lung; Rodentia; Granulomatosis; Inflammation; Respiratory system; Silica; Inhalation; Vertebrata; Mammalia; Animal; Infiltration; Silicosis
• ISSN: 0190-2148; 1521-0499
• DOI: 10.1080/019021401753181845

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 F(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.