Characterization of Platelet-Monocyte Complexes in HIV-1 Infected Individuals: Possible Role in HIV-associated Neuroinflammation1

HIV-1-associated neuroinflammation persists even with effective combined anti-retroviral therapy (cART), and is associated with the presence of activated monocytes/macrophages within the CNS. In order to infiltrate the CNS, monocytes transmigrate across the selectively permeable blood brain barrier (BBB), which is compromised during HIV infection. Interestingly, platelet-derived excess soluble CD40L (sCD40L) found in the plasma and cerebrospinal fluid (CSF) of HIV-1 infected individuals with cognitive impairment has previously been implicated in increased BBB permeability. Here we show that sCD40L also promotes the formation of complexes between inflammatory monocytes and activated platelets (PMCs), which are detected by flow cytometry as monocytes that express excess of CD61, a platelet marker and that these complexes are increased in individuals with HIV infection. PMCs exhibit an enhanced ability to adhere to human brain microvascular endothelial cells as compared to monocytes alone and migrate across transendothelial barrier. These complexes can be found marginalized in the lumen of post-capillary venules in post-mortem brain tissue derived from cases of HIV-1-associated encephalitis (HIV-E). The extravasation of monocytes across the brain endothelium may exacerbate neuroinflammation, indicating that enhancing this event via platelet interaction may be a contributing factor in the development of cognitive impairment. Thus, dampening platelet activation, and in turn PMC formation, with anti-platelet agents may prove beneficial in developing adjunctive therapies for use in combination with cART in an effort to reduce HIV-1-associated neurological deficit