The role of leukocytes during acute phase inflammation in crystalline silica-induced lung injury.

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.