Downstream Signaling Events

In contrast to the increase in adhesion following the activation of Src-family kinases and possibly an ecto-alkaline phosphatase, activation of the ERK 1/2 and p38 MAP kinase pathways had no immediate effect on IRBC adhesion. However, this lack of effect of MAP kinases on adhesion does not exclude an important downstream role for MAP kinases in regulating gene expression of molecules induced as a result of PfEMP1 ligation of CD36, including cytokines and chemokines that would in turn modulate the adhesion process. The occurrence of downstream effects of MAP kinases would be consistent with the observation that the

ERK 1/2 and the p38 MAPK pathways are activated in monocytes following CD36 cross-linking with OKM5, and blockade of these pathways result in inhibition of phagocytosis of IRBCs. In dendritic cells (DC), the binding of IRBC to surface-expressed CD36 leads to a switch in production of IL-12 to IL-10, and an associated inability to activate T cells. Recently, apoptosis in lung microvascular endothelial cells has been observed after the cells were cocultured with IRBCs. However, the percentage of apoptotic cells appears to be limited (~15%), which might explain the absence of widespread endothelial damage in patients with severe fal-ciparum malaria. Collectively, these findings suggest that the interaction of IRBCs with host cells can result in profound modulation of their normal function.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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