Delayed clearance of zymosan-induced granuloma and depressed phagocytosis of macrophages with concomitant up-regulated kinase activities of Src-family in a human monocyte chemoattractant protein-1 transgenic mouse
| Autor: | Akio Takahashi, Toshiaki Takayanagi, Chikako Iwabuchi, Izumi Negishi, Hiroshi Ishikura, Enkh-Amar Dondog, Kouji Matsushima, Naofumi Mukaida, Masahito Kato, Kazuya Iwabuchi, Kazumasa Ogasawara, Kazunori Onoé, Keiko Watano, Shigetsugu Hatakeyama, N. Matsuki, Hiroki Nishihori, Manabu Ato |
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| Předmět: |
Genetically modified mouse
Lymphoid Tissue Phagocytosis Immunology Mice Transgenic Biology Nitric Oxide Mice chemistry.chemical_compound In vivo Proto-Oncogene Proteins medicine Animals Ascitic Fluid Humans Immunology and Allergy Protein kinase A Chemokine CCL2 Mice Inbred C3H Granuloma Kinase Monocyte Zymosan Neoplasms Experimental Hematology Protein-Tyrosine Kinases Molecular biology Up-Regulation Mice Inbred C57BL src-Family Kinases medicine.anatomical_structure chemistry Macrophages Peritoneal Proto-Oncogene Proteins c-hck Cancer research Ex vivo |
| Zdroj: | ResearcherID Scopus-Elsevier |
| Popis: | A human monocyte chemoattractant protein-1 (hMCP-1) transgenic mouse (Tgm) line which constitutively produces a large amount of hMCP-1 (7-13 ng/ml in the serum) was established. Although expression of the transgene was detected in various tissues, an accumulation of macrophages (Mphi) was seen in only lymphoid organs which might be attributed to the high concentration of hMCP-1 in these organs. A reduced phagocytosis by peritoneal Mphi in vivo and a delayed clearance of granulomas in the liver following zymosan administration were observed in these Tgm. However, peritoneal exudate cells (PEC) from Tgm exhibited normal in vitro phagocytic activity and nitric oxide (NO) production upon stimulation with IFN-gamma as compared with those from non-Tgm. In addition, high activities of src-family protein tyrosine kinases (PTK), Fgr and Hck, were also noted in the peritoneal resident cells from Tgm, whereas the level of mitogen-activated protein kinase (MAPK) activity was almost the same as that of non-Tgm. It was suggested that the low functional activities of Tgm Mphi seen in vivo were attributed to down-regulation of the unique transducing system of hMCP-1 signals under the influence of a high concentration of the hMCP-1. It seemed that the depressed functions were recovered when the peritoneal cells were released ex vivo from such a high hMCP-1 environment. |
| Databáze: | OpenAIRE |
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