Altered Monocyte and Endothelial Cell Adhesion Molecule Expression Is Linked to Vascular Inflammation in Human Immunodeficiency Virus Infection

Abstract

Background.Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium.Methods.Monocyte subsets (CD14+CD16−, CD14+CD16+, CD14DimCD16+) from HIV negative (HIV−) and antiretroviral therapy-treated HIV positive (HIV+) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2]) inflammation were measured by enzyme-linked immunosorbent assay.Results.Proportions of CD16+ monocyte subsets were increased in HIV+ participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV+ participants (P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA2 were also increased in HIV+ participants (P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV+ participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA2 (P < .05 for all).Conclusions.Increased proportions of CD16+ monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection.

Macrophages and Phospholipases at the Intersection between Inflammation and the Pathogenesis of HIV-1 Infection

“…Monocytes from infected individuals show a spontaneous overproduction of ROS [ 98 ]. An increased proportion of CD16 + monocytes, as well as an altered expression of adhesion molecules (ICAM-1, VCAM-1, and LFA-1) and chemokine receptors on monocytes and endothelial cells, are linked to vascular inflammation in HIV-1 infection [ 99 ]. Expression of sCD163, sCD14, fractalkine, TNFR-II, IL-6 and Lp-PLA 2 are also increased in HIV-1-infected individuals and do not return to normal levels under HAART [ 93 , 99 ].…”

“…An increased proportion of CD16 + monocytes, as well as an altered expression of adhesion molecules (ICAM-1, VCAM-1, and LFA-1) and chemokine receptors on monocytes and endothelial cells, are linked to vascular inflammation in HIV-1 infection [ 99 ]. Expression of sCD163, sCD14, fractalkine, TNFR-II, IL-6 and Lp-PLA 2 are also increased in HIV-1-infected individuals and do not return to normal levels under HAART [ 93 , 99 ]. In particular, the proportion of individuals with Lp-PLA 2 levels ≥200 ng/mL is dramatically increased among HIV-1 + (61%) compared to HIV-1 − (21%) persons, in spite of similar levels of triglycerides, LDL, and oxidized LDL between the groups [ 99 ].…”

“…Expression of sCD163, sCD14, fractalkine, TNFR-II, IL-6 and Lp-PLA 2 are also increased in HIV-1-infected individuals and do not return to normal levels under HAART [ 93 , 99 ]. In particular, the proportion of individuals with Lp-PLA 2 levels ≥200 ng/mL is dramatically increased among HIV-1 + (61%) compared to HIV-1 − (21%) persons, in spite of similar levels of triglycerides, LDL, and oxidized LDL between the groups [ 99 ]. Higher expression levels or increased enzymatic activity of Lp-PLA 2 and sPLA 2 are consistently found in HIV-1-infected patients compared to healthy controls.…”

p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation

“…Cases of acute coronary thrombosis in HIV positive individuals also occur often at young ages 50 . Concurrent activation of platelets, monocytes and EC by p17 from HIV-most certainly promotes a thrombotic inflammatory environment that might pre-dispose these individuals to early onset AMI 51 . Hence, previous findings of the pro-monocytic activation of p17 52 , platelet aggregating and tissue factor stimulation (submitted elsewhere) and here, angiogenic capabilities, indicate a mechanism through which this co-morbidity could develop.…”

Editorial: Gateway to monocyte entry into the brain: CXCR7, the new orchestra conductor

“…1). These two populations differ in a variety of ways, which include cell surface markers, cytokine production, and cell lifespan [2,3]. Remarkably, CD14 + CD16 + monocytes, in contrast to the more abundant CD14 + CD16 2 monocytes, transmigrate across the BBB at low homeostatic levels of CXCL12.…”