Detection of circulating platelet–monocyte complexes in persons infected with human immunodeficiency virus type-1

Abstract

Activated platelets form transient aggregates with monocytes in circulation and have a half-life of approximately 30–60 minutes. These complexes are increased in various inflammatory conditions and are an early marker of myocardial infarction. HIV-1 infection is associated with chronic inflammation, and increased CD16+ inflammatory monocytes have been observed in these individuals, probably as a result of increased interaction with platelets. However, narrow detection period and platelet activation during sample processing pose significant problems in detecting platelet-monocyte complexes (PMCs). A method was standardized addressing these difficulties, to enumerate PMCs involving CD16+ or CD16− monocytes in whole blood using flow cytometry. Blood collected from healthy individuals was treated with either collagen (for platelet activation) or LPS (for monocyte activation) and subsequently used to study effect of these treatments on PMC formation. This method was also validated for the ex vivo quantitation of PMCs in blood obtained from persons infected with HIV. The in vitro results demonstrated that platelet activation, but not monocyte activation, resulted in significant increase in PMC formation. There was a significant increase in CD16+ PMCs and platelet activation, in samples obtained from persons infected with HIV as compared to those without HIV infection. Furthermore, PMC percentages correlated positively with platelet activation. These findings improve the ability to detect PMCs and shed light on HIV pathogenesis.

Emerging roles for platelets as immune and inflammatory cells

“…158,159 Furthermore, platelet-monocyte aggregates are greatly increased in the circulation of both infected primates and humans, and platelets may induce monocyte differentiation into a more inflammatory phenotype. 159,160 Thrombocytopenia is associated with increased neurologic complications of HIV infection, and neuro-HIV is hypothesized to be driven by infected macrophage migration into the brain. 158,160,161 This has led some to speculate that a platelet-induced macrophage inflammatory phenotype may accelerate neurologic complications of HIV infection, but much remains to definitively demonstrate this.…”

“…159,160 Thrombocytopenia is associated with increased neurologic complications of HIV infection, and neuro-HIV is hypothesized to be driven by infected macrophage migration into the brain. 158,160,161 This has led some to speculate that a platelet-induced macrophage inflammatory phenotype may accelerate neurologic complications of HIV infection, but much remains to definitively demonstrate this. Influenza also exerts a large public health impact every year.…”

Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

“…However, other groups have reported that the formation of MPA is primarily dependent on platelet activation and to a lesser extent on monocyte activation. 26,44,45 Therefore, we speculated that the increased monocyte activation in HIV-1 infection might be partially ascribed to MPA formation, which rendered monocytes more active, more adhesive, more procoagulant, and more inflammatory through the release of pro-inflammatory cytokines (such as IL-6 and tumor-necrosis factor-a) or the expression of tissue factor, resulting in an increased CVD risk. In summary, we showed for the first time that MPA levels are increased on CD14 …”

“…Increased MPA formation was previously reported in HIV-1-infected patients receiving antiretroviral therapy and in simian immunodeficiency virus infection. 25,26 However, the MPA levels in HIV-1-infected, treatment naive patients and the changes in MPA levels as the disease progresses have not been previously examined. Although monocyte activation is a typical characteristic of HIV-1 infection, the association between monocyte activation and MPA levels in HIV-1 infection is still unclear.…”

Estudo de fase I/II de uma terapia celular para HIV baseada em células dendríticas autólogas pulsadas com vírus autólogos quimicamente inativados

“…Uma possível explicação para este problema seria a formação de agregados de plaquetas e monócitos, frequente nos indivíduos infectados pelo HIV (179) e que dificultaria o processo de separação dos monócitos das outras células, feito por aderência em superfície plástica. Outro fenômeno observado foi a apoptose precoce dos monócitos em cultura o que poderia estar relacionado ao grau de ativação celular do indivíduo infectado, levando à morte celular induzida por ativação (activation-induced cell death) (180)(181)(182) .…”