C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental MalariaReport as inadecuate




C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria - Download this document for free, or read online. Document in PDF available to download.

Background

Placental malaria PM is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes PEs and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.

Methodology and Principal Findings

Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI pfGPI enhanced C5a receptor expression CD88 on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines IL-6, TNF, IL-1β, and IL-10, chemokines IL-8, MCP-1, MIP1α, MIP1β and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.

Conclusions and Significance

These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function.



Author: Andrea Conroy, Lena Serghides, Constance Finney, Simon O. Owino, Sanjeev Kumar, D. Channe Gowda, W. Conrad Liles, Julie M. Moore,

Source: http://plos.srce.hr/



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