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December 1, 1995The Journal of Immunology386 citationsOpen Access

Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1

MFMaría E. FuentesSDStephen K. DurhamMSMavis R. Swerdel

Key Points

  • To evaluate how targeted transgenic overexpression of monocyte chemoattractant protein-1 (MCP-1) in the thymus and central nervous system directs leukocyte recruitment.
  • Generated transgenic mice overexpressing MCP-1 selectively in the thymus and central nervous system.
  • Characterized recruited cells using light microscopy, ultrastructural criteria, and immunohistochemistry for Mac-1 and F4/80 markers.
  • Administered lipopolysaccharide (LPS) treatment to assess inflammatory potentiation of cell recruitment.
  • Transgenic mice exhibited higher mononuclear cell counts in target tissues, with a modest increase in Mac-1- and F4/80-positive cells in the thymus and extensive infiltration in the brain.
  • Recruited brain cells were predominantly monocytes and macrophages clustered in a perivascular orientation with minimal parenchymal infiltration, matching vessel MCP-1 accumulation.
  • Systemic LPS administration significantly amplified the magnitude of mononuclear cell infiltration into the brain.

Abstract

Transgenic mice overexpressing the chemokine monocyte chemoattractant protein-1 (MCP-1) in the thymus and central nervous system have a higher number of mononuclear cells in those tissues than do control littermates. In the thymus, there is a modest increase in the number of Mac-1 and F4/80 positive cells, but no apparent change in the number of lymphoid cells. A more pronounced mononuclear infiltrate is detected in transgenic mice expressing MCP-1 in the brain. The vast majority of the recruited cells in the brain are monocytes and macrophages, as defined by light microscopy, and ultrastructural and immunohistochemical criteria. Such cells are found in a perivascular orientation with minimal parenchymal infiltration, possibly as a consequence of the accumulation of MCP-1 in the vessels, as shown by immunohistochemistry. The mononuclear cell infiltrate in the brain can be significantly amplified by LPS treatment, suggesting that the recruitment properties of MCP-1 can be potentiated by additional factors.

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Cite This Study

Fuentes et al. (1995) studied this question.

synapsesocial.com/papers/69de7e4d6e50a6aba3e93ee2https://doi.org/10.4049/jimmunol.155.12.5769
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