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

Silicosis is characterized by progressive granulomatous and fibrogenic resp onse in the lung. Inhaled crystalline silica (Qt) induces activation of pul monary macrophages and leukocyte infiltration in the lung of Qt-treated ani mals. We investigated the role of leukocyte infiltration and L-selectin dur ing the acute phase of inflammation in developing chronic lung injury in Qt -treated rats. Seventy Wistar male rats were treated with a single transtra cheal instillation of Qt (25 mg/kg). Rats were treated intraperitoneally wi th anti L-selectin monoclonal antibody (mAb), F(ab')2 HRL-3 (HRL-3, a block ing mAb), or F(ab')2 HRL-2 (HRL-2, a non-blocking mAb) for 4 days before an d after Qt injection. Administration of HRL-3 reduced approximately 50% of leukocyte infiltration in the BAL, whereas HRL-2 treatment prior to Qt stim ulation showed time-dependent increase of BAL leukocytes. CINC and GRO leve ls as well as peripheral blood cell counts were similar in HRL-2- ar HRL-3- treated animals in the first 4 days of the study. Three months after Qt tre atment, extensive granuloma-containing macrophages and leukocytes developed in thc lung of the HRL-3-treated rats as compared with the HRL-2-treated r ats. 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 leukocy te 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.