Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins

Tao Tang, Paul S. Frenette, Richard O. Hynes, Denisa D. Wagner, Tanya N. Mayadas

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Leukocyte accumulation in cerebrospinal fluid and disruption of the blood- brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine- induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/μl as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P- and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P- and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P- and E-selectins cooperatively contribute to meningitis and that functional blocking of both endothelial selectins in conjunction with antibiotics may provide a therapeutic approach for treatment of bacterial meningitis.

Original languageEnglish (US)
Pages (from-to)2485-2490
Number of pages6
JournalJournal of Clinical Investigation
Volume97
Issue number11
DOIs
StatePublished - Jun 1 1996
Externally publishedYes

Keywords

  • blood-brain barrier
  • cerebrospinal fluid
  • endothelium
  • inflammation
  • leukocytes

ASJC Scopus subject areas

  • Medicine(all)

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