Augmented expression of tumour necrosis factor-alpha induced by lipopolysaccharide in spleen of human monocyte chemoattractant protein-1 transgenic mouse enhances the lipopolysaccharide sensitivity of the marginal zone macrophages


Ato, M; Iwabuchi, K; Shimada, S; Mukaida, N; Onoe, K; (2002) Augmented expression of tumour necrosis factor-alpha induced by lipopolysaccharide in spleen of human monocyte chemoattractant protein-1 transgenic mouse enhances the lipopolysaccharide sensitivity of the marginal zone macrophages. Immunology, 106 (4). pp. 554-63. ISSN 0019-2805 DOI: https://doi.org/10.1046/j.1365-2567.2002.01450.x

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Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a protective cytokine in murine endotoxaemia induced by lipopolysaccharide (LPS). In this study, LPS-induced pathophysiology in the human (h) MCP-1 transgenic mouse (Tgm) line was investigated. The hMCP-1 Tgm showed a marked increase in the mortality and weight loss following LPS administration. In the Tgm spleens, disappearance of marginal zone macrophages (MZMphi) and dendritic cells (DC) was induced by a smaller amount of LPS than that required for the disappearance in non-transgenic littermates. A significant number of apoptotic cells were seen in these areas. Furthermore, expressions of tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and IL-6 mRNA were enhanced and sustained in the LPS-treated Tgm. Neutralization of TNF-alpha considerably depressed the LPS-sensitivity of Tgm. These findings demonstrate that the continuous and systemic presence of MCP-1 is no more protective toward endotoxaemia and suggest that the high sensitivity of the MZMphi and DC to LPS is attributed to the enhanced TNF-alpha production in the hMCP-1 Tgm.

Item Type: Article
Keywords: Animal, Apoptosis/immunology, Cytokines/genetics/metabolism, Dendritic Cells/immunology, Endotoxemia/*immunology, Gene Expression, Human, Interleukin-1/metabolism, Lipopolysaccharides/*immunology, Macrophages/*immunology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocyte Chemoattractant Protein-1/genetics/*immunology, RNA, Messenger/genetics, Spleen/immunology, Support, Non-U.S. Gov't, Tumor Necrosis Factor/*metabolism, Animal, Apoptosis, immunology, Cytokines, genetics, metabolism, Dendritic Cells, immunology, Endotoxemia, immunology, Gene Expression, Human, Interleukin-1, metabolism, Lipopolysaccharides, immunology, Macrophages, immunology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Monocyte Chemoattractant Protein-1, genetics, immunology, RNA, Messenger, genetics, Spleen, immunology, Support, Non-U.S. Gov't, Tumor Necrosis Factor, metabolism
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 12153519
Web of Science ID: 177195600015
URI: http://researchonline.lshtm.ac.uk/id/eprint/18299

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