Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria.

Abstract

Some patients with Plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. Plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [ESM]), and infected mice exhibit a systemic inflammatory response. Because platelets are proposed to contribute to ESM and other systemic inflammatory responses, we determined whether platelet adherence contributes to experimental malarial pathogenesis. Indeed, a significant (P < 0.005) increase in the number of rolling and adherent platelets was observed by intravital microscopy in brain venules of P. berghei-infected mice compared with the number in uninfected controls. P-selectin- or ICAM-1-deficient mice exhibit increased survival after P. berghei infection. We observed a significant (P < 0.0001) reduction in the morbidity of mice injected with anti-CD41 (alpha(IIb) or gpIIb) monoclonal antibody on day 1 of P. berghei infection compared with the morbidity of infected controls injected with rat immunoglobulin G. Additionally, platelet rolling and adhesion in brain venules were reduced in P. berghei mice lacking either P-selectin or ICAM-1 or when the platelets were coated with anti-CD41 monoclonal antibody. Unlike other inflammatory conditions, we did not detect platelet-leukocyte interactions during P. berghei malaria. Because (i). leukocyte adhesion is not markedly altered in the absence of P-selectin or ICAM-1 and (ii). CD41 is not an adhesion molecule for parasitized erythrocytes, these findings support the hypothesis that inhibition of platelet adhesion to the brain microvasculature protects against development of malarial pathogenesis.

• Authors: Guang Sun, Wun-Ling Chang, Jie Li, Seth Mark Berney, Donald Kimpel, Henri C van der Heyde
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 11 Pg. 6553-61 (Nov 2003) ISSN: 0019-9567 [Print] United States
• PMID: 14573677 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• P-Selectin
• Platelet Membrane Glycoprotein IIb
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Brain (blood supply)
• Cell Communication
• Endothelial Cells (physiology)
• Female
• Intercellular Adhesion Molecule-1 (physiology)
• Malaria, Cerebral (prevention & control)
• Mice
• Mice, Inbred C57BL
• Microcirculation
• P-Selectin (physiology)
• Plasmodium berghei
• Platelet Adhesiveness
• Platelet Membrane Glycoprotein IIb (physiology)