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Pulmonary Drug Discovery & Therapy (Track)



ANTIFIBROTIC EFFECTS OF RESERPINE ON LUNG FIBROSIS. HAEMATOPOIETIC STEM CELLS IN THE PATHOGENESIS OF PNEUMOFIBROSIS

Evgenij Germanovich Skurikhin, E.S. Khmelevskaya, O.V. Pershina, N.N. Ermakova, V.A. Krupin, L.A. Ermolaeva, V.D. Yakushina, A.M. Reztsova, V.M. Reztsova, I.E. Stepanova and A.M. Dygai

Laboratory of Pathological Physiology and Experimental Therapy, Institute of Pharmacology of RAMS SD Tomsk, Russia


Abstract:


In this study was found, that inflammation in interstitial lung tissue of mice C57BL/6 after intratracheal injection of the bleomycin supported by the bone marrow and circulating in blood cells with the phenotype Sca-1+, c-Kit+, CD34-, (CD3, CD45R (B220), Ly6C, Ly6G (Gr1), CD11b (Mac1), TER-119)- (hematopoietic stem cells (HSCs)) and progenitor hematopoietic cells (granulocyte-erythroidmacrophage- megakaryocytic (CFU-GEMM) and granulocyte precursors (CFU-G)). These results demonstrate that the intraperitoneal injection of reserpine reduces infiltration of alveolar interstitium and alveolar passages by inflammatory cells and prevents the growth of connective tissue in the lung parenchyma. Supposedly, the antiinflammatory effect of reserpine caused by reduced activity the differentiation of bone marrow HSCs in CFU-G, a decrease of circulating HSCs and progenitor hematopoietic cells and the violation of their migration in bleomycin-treated lungs. These data suggest that the decrease caused by the reserpine in deposition of collagen fibers in the lung''s parenchyma associated with a decrease in the inflow of multipotent mesenchymal stromal cells (MSCs) and progenitor fibroblast bone marrow-derived cells to lungs. Thus, reserpine violates the differentiation of MSCs into fibroblast-like cells.