Figure 1

Working model and overall summary. Upon exposure to HIV effector molecules, both viral and host derived, platelets become aberrantly activated and release an excess of soluble CD40 ligand (sCD40L). This sCD40L can then bind to its receptor, CD40, on the surface of brain microvascular endothelial cells (BMVECs), inducing an inflammatory endothelial cell phenotype. Features of this phenotype include upregulation of cellular adhesion molecules such as P-selectin, ICAM-1 and VCAM-1, as well as the release of the chemoattractant MCP-1. Subsequently, leukocytes are recruited to the endothelium, where they are able to adhere and migrate through the barrier and into the central nervous system, thus stimulating a pro-inflammatory, excitotoxic environment. Therefore, inhibition of sCD40L release from platelets via antiplatelet therapies has the potential to attenuate this process. BMVEC, brain microvascular endothelial cell; cART, combined antiretroviral therapy; ICAM-1, intracellular adhesion molecule 1; sCD40L, soluble CD40 ligand; VCAM-1, vascular cell adhesion molecule 1.