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 Citations (Scopus)

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
StatePublished - Jun 1 1996
Externally publishedYes

Fingerprint

Selectins
P-Selectin
Meningitis
E-Selectin
Cytokines
Leukocytes
Cerebrospinal Fluid
Blood-Brain Barrier
Leukocyte-Adhesion Receptors
Permeability
Leukocyte Rolling
Bacterial Meningitides
Anti-Bacterial Agents
Inflammation
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. / Tang, Tao; Frenette, Paul S.; Hynes, Richard O.; Wagner, Denisa D.; Mayadas, Tanya N.

In: Journal of Clinical Investigation, Vol. 97, No. 11, 01.06.1996, p. 2485-2490.

Research output: Contribution to journalArticle

Tang, Tao ; Frenette, Paul S. ; Hynes, Richard O. ; Wagner, Denisa D. ; Mayadas, Tanya N. / Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 11. pp. 2485-2490.
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