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Late administration of monoclonal-antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria

Academic Article
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Overview

authors

  • Grau, G. E.
  • Pointaire, P.
  • Piguet, P. F.
  • Vesin, C.
  • Rosen, Hugh
  • Stamenkovic, I.
  • Takei, F.
  • Vassalli, P.

publication date

  • September 1991

journal

  • European Journal of Immunology  Journal

abstract

  • We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Brain
  • Cell Adhesion Molecules
  • Disease Models, Animal
  • Hypothermia
  • Intercellular Adhesion Molecule-1
  • Lymphocyte Function-Associated Antigen-1
  • Malaria
  • Male
  • Mice
  • Mice, Inbred CBA
  • Plasmodium berghei
  • Tumor Necrosis Factor-alpha
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Identity

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.1830210939

PubMed ID

  • 1679717
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Additional Document Info

start page

  • 2265

end page

  • 2267

volume

  • 21

issue

  • 9

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