Increased levels of reactive oxygen species in platelets and platelet-derived microparticles and the risk of respiratory failure in HIV/AIDS patients

Abstract

Respiratory failure (RF) is the main cause of hospital admission in HIV/AIDS patients. This study assessed comorbidities and laboratory parameters in HIV/AIDS inpatients with RF (N = 58) in relation to those without RF (N = 36). Tuberculosis showed a huge relative risk and platelet counts were slightly higher in HIV/AIDS inpatients with RF. A flow cytometry assay for reactive oxygen species (ROS) showed lower levels in platelets of these patients in relation to the healthy subjects. However, when stimulated with adrenaline, ROS levels increased in platelets and platelet-derived microparticles of HIV/AIDS inpatients, which may increase the risk of RF during HIV and tuberculosis (HIV-TB) coinfection.

Challenges in Platelet Functions in HIV/AIDS Management

“…Although HIV-associated platelets display increased baseline expression of surface activation markers compared to healthy controls [32], there is evidence of refractoriness to further agonist stimulation. This behavior has been referred to as "platelet exhaustion" in many publications [25,28,32,37,38].…”

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis

“…Where one treatment in a disease with increased LPS may help prevent PEV activity, the same treatment in a disease with increased SSL5 may have no effect or could even have a negative effect. For example, if patients are given adrenaline, their PEVs contain more dihydroethidium (DHE) fluorescence, indicating more ROS production [ 106 ]. Studies in future should focus on better characterization to understand the mechanistic activities of PEVs under different disease conditions and how different pathogenic stimuli are affecting PEV production and formulation.…”

“…Falasca et al identified that some proteins involved in the thrombotic response of PEVs are apolipoprotein E (APOE), Beta-2-glycoprotein 1 (APOH), complement component 3 (C3), complement component 5 (C5), complement factor H (CFH), complement factor H-related protein 1 (CFHR1), factor 2 (F2), fibrinogen alpha (FGA), fibrinogen beta (FGB), fibrinogen gamma (FGG), histidine-rich glycoprotein (HRG), kininogen-1 (KNG1), plasminogen (PLG), and antithrombin-III (SERPINC1) [ 192 ]. It has also been found that PEVs in HIV have higher numbers that are positive for dihydroethidium (DHE), indicating that they contain ROS [ 106 ]. Unexpectedly, even though there is increased ROS, these PEVs actually have lower mitochondria [ 9 ], suggesting sources other than mitochondria induce ROS production in PEVs in HIV.…”

Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children

“…HIV infection has been shown to have a dual effect on neutrophil functions as well. On the one hand, HIV infection leads to functional impairment of neutrophils in the form of reduced chemotaxis, cytokine production, decreased degranulation, impaired production of ROS, and impaired antibody-mediated cytotoxicity [ 8 , 9 ]; on the other hand, HIV infection has been shown to delay apoptosis of neutrophils [ 10 ], as well as, cause hyperactivation of neutrophils associated with an increased production of proinflammatory cytokines [ 11 ] and increased ROS production leading to chronic systemic inflammation [ 12 , 13 ]. ROS also contributes to HIV pathogenesis, disease progression, and transmission [ 14 ].…”

“…Upregulation of neutrophil inflammasome in HIV-infected individuals has been shown to contribute to persistent inflammation and immunological nonresponse [ 15 ] as well as increased morbidity [ 16 ]. The effect of HIV infection on neutrophil oxidative burst and phagocytic functions have also been inconsistent [ 8 , 9 , 12 , 13 ]; moreover, these have been evaluated only sparingly in children living with HIV (CLHIV) [ 9 , 17 – 20 ]. Further, the effect and duration of ART on reversing the neutrophil dysfunction has been inconsistent [ 11 , 21 – 23 ].…”