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First published online August 30, 2007
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2007-0508v1
25/12/3165    most recent
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Submitted on June 27, 2007
Accepted on August 21, 2007

TISSUE-SPECIFIC STEM CELLS

Irradiation Does not Compromise or Exacerbate the Innate Immune Response in the Brain of Mice that were Transplanted with Bone Marrow Stem Cells

Nicolas P. Turrin 1, Marie Michèle Plante 1, Martine Lessard 1, Serge Rivest 1*

1 Laboratory of Molecular Endocrinology, CHUL Research Center, Department of Anatomy and Physiology, Laval University, 2705, Laurier Boulevard, Québec City, Qc., Canada, G1V 4G2

* To whom correspondence should be addressed. E-mail: Serge.Rivest{at}crchul.ulaval.ca.


   Abstract

Microglia and invading macrophages play key roles in the brain immune response. The contributions of these two populations of cells in health and diseases have yet to be clearly established. The use of chimeric mice receiving bone marrow-derived stem cell grafts from green fluorescent protein(GFP)-expressing mice has provided an invaluable tool to distinguish between local and blood-derived monocytic populations. The validity of the method is questioned because of the possible immune alterations caused by the irradiation of the recipient mouse. In this experiment, we compared the brain expression of innate immune markers Toll-like receptor 2, interleukin-1{beta}, tumor necrosis factor-{alpha} and monocyte chemoattractant protein-1 in C57BL/6, GFP and chimeric mice following an intracerebral injection of lipopolysaccharide. The endotoxin caused a marked transcriptional activation of all these innate immune genes in microglial cells across the ipsilateral side of injection. The expression patterns and signal intensity were similar in the brains of the three groups of mice. Consequently, the chimera technique is appropriate to study the role of infiltrating and resident immune cells in the brain without having immune compromised hosts.

Key Words. Chimeric mice, neuroinflammation, microglia, macrophages, irradiation, green fluorescent protein.




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