Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Development, differentiation, and maturation of Kupffer cells

Abstract: Primitive macrophages first develop in the murine and human yolk sac and then differentiate into fetal macrophages. Primitive or fetal macrophages enter the blood stream and migrate into the fetal liver. Fetal macrophages possess a high proliferative capacity and express antigens and peroxidase activity of resident macrophages with the progress of gestation; they become mature and then transform into Kupffer cells. In contrast, myelopoiesis and monocytopoiesis are not active in yolk sac hematopoiesis and in the early stages of hepatic hematopoiesis. Precursor cells of primitive or fetal macrophages exist and granulocyte/macrophage colony-forming cells develop in the yolk sac and in the early stages of fetal liver development, whereas macrophage colony-forming cells emerge and increase later in fetal liver development. In vitro, similar colonies were formed from each fetal hematopoietic cell in the presence of different macrophage growth factors. During culturing of the yolk sac cells and hepatic hematopoietic cells on a monolayer of mouse stromal cell line, ST2, primitive or fetal macrophage colonies developed before the formation of monocyte colonies, suggesting the existence of a direct pathway of differentiation from primitive macrophages into fetal macrophages during ontogeny. In severely monocytopenic mice induced by the administration of strontium-89, Kupffer cells have a proliferative capacity and are maintained by self-renewal. In macrophage colony-stimulating factor (M-CSF)-deficient (op/op) mice, the number of Kupffer cells is reduced, and they are characterized by immature morphology and a proliferative potential similar to that of primitive or fetal macrophages during ontogeny. Immediately after the administration of M-CSF to op/op mice, Kupffer cells start proliferating and become mature. This finding indicates that M-CSF plays an important role in the differentiation and proliferation of Kupffer cells. Microsc. Res. Tech. 39:350– 364, 1997. © 1997 Wiley-Liss, Inc.

C‐C chemokine receptor 2 (CCR2) deficiency improves bleomycin‐induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage‐derived matrix metalloproteinases

Abstract: Macrophage infiltration is implicated in various types of pulmonary fibrosis One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages In this study, C-C chemokine receptor 2-deficient (CCR2-/-) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 -/- mice demonstrate defective macrophage migration Pulmonary fibrosis was induced in CCR2-/- and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7 Between days 3 and 21, however, BAL fluid from CCR2-/- mice contained fewer macrophages than BAL fluid from CCR2+/+ mice Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2-/- mice Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2-/- mice at day 3 Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2-/- mice At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2-/- mice These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production