Histamine H(3) receptor-mediated signaling protects mice from cerebral malaria.

Abstract

BACKGROUND:

Histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. In humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. We reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (CM) in mice infected with Plasmodium berghei ANKA. Histamine exerts its biological effects through four different receptors designated H1R, H2R, H3R, and H4R.

PRINCIPAL FINDINGS:

In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM. We observed that the lack of H3R expression (H3R(-/-) mice) accelerates the onset of CM and this was correlated with enhanced brain pathology and earlier and more pronounced loss of blood brain barrier integrity than in wild type mice. Additionally tele-methylhistamine, the major histamine metabolite in the brain, that was initially present at a higher level in the brain of H3R(-/-) mice was depleted more quickly post-infection in H3R(-/-) mice as compared to wild-type counterparts.

CONCLUSIONS:

Our data suggest that histamine regulation through the H3R in the brain suppresses the development of CM. Thus modulating histamine signaling in the central nervous system, in combination with standard therapies, may represent a novel strategy to reduce the risk of progression to cerebral malaria.

• Authors: Walid Beghdadi, Adeline Porcherie, Bradley S Schneider, Séverine Morisset, David Dubayle, Roger Peronet, Michel Dy, Jacques Louis, Jean-Michel Arrang, Salaheddine Mécheri
• Journal: PloS one (PLoS One) Vol. 4 Issue 6 Pg. e6004 (Jun 23 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19547708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Histamine H3
• Histamine

Topics

• Animals
• Brain (immunology, metabolism, parasitology)
• Disease Progression
• Female
• Histamine (metabolism)
• Immune System
• Inflammation
• Malaria, Cerebral (metabolism, parasitology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Biological
• Plasmodium berghei (metabolism)
• Receptors, Histamine H3 (metabolism)
• Signal Transduction