If the signaling by IRBCs through CD36 on microvascu-lar endothelial cells is analogous to its action in other cell types, we could anticipate that an assembly of membrane receptors might be involved for endothelial cell activation as a result of IRBC adhesion. Integrins are likely candidate receptors for IRBCs on endothelium, as they promote adhesion to other cells and matrix proteins and are often associated physically and functionally with CD36. Indeed, CD36 is known to guide integrins into signaling rafts, and in so doing may regulate integrin function. The antiangiogenic effect of TSP-1 has been shown to involve its binding to endothelial CD36 as well as to a3b1 integrin. On microglial and other myeloid cells, the activation of CD36 by b-fibrillar peptides (amyloid plaque) involves CD36, a6b1 integrin, and the integrin-associated protein CD47. In retinal pigment epithelium, phagocytosis of outer segment (OS) fragments is mediated by CD36 and a^ integrin, but the molecules appear to have different roles. Whereas avb5 acts as the receptor for OS, the interaction with CD36 with resulting dimerization of the molecule is necessary and sufficient to activate the internalization process. Although we have shown that intracellular signals can be generated by the direct binding of PfEMP1 to endothelial CD36, it is conceivable that additional signals could be induced through the interaction of IRBCs with integrins and/or TSP-1, which can in turn interact with CD47 or the matrix protein 0^3 integrin. The engagement of a core of receptors will immobilize IRBCs on the cell surface, leading to focal aggregation of the receptors into a functional complex. In support of this hypothesis, an anti-av antibody has been shown to inhibit IRBC adhesion to HDMEC under flow conditions in vitro. As well, the uptake of apoptotic cells require both CD36 and 0^3 on macrophages.
Was this article helpful?
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.