Morphometric estimates of infiltrative cellular changes during the development of bleomycin-induced pulmonary fibrosis in hamsters

Abstract

The sequence of cellular infiltration into interstitial lung tissue subsequent to intratracheal administration of bleomycin was examined in hamsters. Quantitation of lesions following bleomycin treatment showed a transient increase in the percentage of lung involved, which peaked at 21 days and decreased thereafter. Associated with these lesions was a significant increase in interstitial cell profile density at 21 and 28 days. The total number of cell profiles decreased after 28 days. The cellular composition of the lesion was dominated by monocytes, neutrophils, and macrophages in the initial phase of the fibrosis. Subsequently, monocytes were significantly decreased at 21, 28, and 42 days, as compared with the 7-day value. Similarly, neutrophils were significantly decreased at 21 and 28 days, as compared with the 7-day value. In contrast, macrophages were significantly decreased in the initial phase (7 days) of the cellular infiltration and the later phase at 35 and 42 days, as compared with the value at 4 days after treatment. Lesion composition in the later phase exhibited significant increases in fibroblasts and eosinophils, accompanied by a general increase in lymphocytes. It is concluded that bleomycin-induced inflammatory sequela exhibits temporally based changes in cellular composition of the infiltrate and that the temporal changes in cellularity might be one of the determinants in the pathophysiology of pulmonary fibrosis induced by bleomycin.