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.
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.
Ato
Manabu
M
Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University; Sapporo, Japan. kazunori@imm.hokudai.ac.jp
Iwabuchi
Kazuya
K
Shimada
Shigeki
S
Mukaida
Naofumi
N
Onoé
Kazunori
K
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha