Abstract
Background: HIV infection has been associated with endothelial dysfunction. Endothelial microparticles (EMP) are informative markers of endothelial cell status and can exert transcellular effects in leukocytes. No previous studies have assessed EMP and their interactions with leukocytes in HIV-infected patients.
Methods: We studied 29 patients (mean age = 42.1±7 years) with HIV infection on HAART who demonstrated an optimal viral and immunological response (CD4+ cell count>200 /mm3 and < 50 viral copies/ml by PCR analysis). Patients with diabetes, smoking, thrombotic, cardiovascular or malignant disease were excluded. We used age- and gender-matched healthy controls. Using flow cytometry, we measured free EMP identified by:
Expression of CD31 and lack of expression of CD42b (EMP31); E-selectin expression (EMP62E); CD51 expression (EMP51), or; CD54 expression (EMP54).
EMP62E- and EMP54-leukocyte conjugates were measured based on the detection of E-selectin or CD54, respectively, coexpressed with CD45 in neutrophils, monocytes and lymphocytes.
Results: Results are summarized in Table 1. Levels of free EMP31, EMP51, EMP54 and EMP62E did not differ significantly between the groups. However, a very significant elevation of EMP54-Lymphocyte Conjugates (p=0.001) and a trend towards an elevation of EMP62E-Lymphocyte Conjugates was seen in HIV-infected patients. Furthermore, EMP63E-lymphocyte conjugates significantly correlated with the CD4+ cell count (R=-0.64; p=0.03). Conversely, HIV-infected patients demonstrated significantly lower levels of EMP62E -Monocyte Conjugates (p=0.0005) and a trend toward lower levels of EMP54 -Monocyte Conjugates (p=0.08).
Conclusions: HIV infected patients with optimal response to HAART demonstrate an increased number of circulating EMP-lymphocyte conjugates with decreased number of EMP-monocyte conjugates. We speculate that viral EMP-receptor upregulation in lymphocytes and/or downregulation in monocytes could account for this phenomenon. EMP-lymphocyte conjugates inversely correlate with the CD4 count. The role of increased EMP-lymphocyte interactions in viral spread and lymphocyte dysfunction/apoptosis in HIV infected-patients requires further investigation.
Levels of endothelial microparticles (EMPs) and EMP-leukocyte conjugates in HIV+ patients compared to controls. HIV+ Patients Control P value MFI=Mean fluorescence intensity EMP31, counts/μL (IQR) 680 (497–1112) 1018 (566-1691) 0.16 EMP51, counts/μL (IQR) 114 (75–141.5) 114 (96–143) 0.59 EMP62E, counts/μL (IQR) 72 (53.5–123.5) 77 (48–113) 0.66 EMP54, counts/μL (IQR) 58 (39.5–78.5) 39 (18–141) 0.42 EMP54-Lymphocyte Conjugates, MFI (IQR) 1.37 (1.26–1.42) 1.2 (1.13–1.26) 0.001 EMP54-Monocyte Conjugates, MFI (IQR) 1.14 (1.05–1.3) 1.22 (1.16–1.64) 0.08 EMP54-Neutrophil Conjugates, MFI (IQR) 1.46 (1.27–2.28) 1.66 (1.28–2.34) 0.74 EMP62E-Lymphocyte Conjugates, MFI (IQR) 1.15 (1.11–1.19) 1.13 (1.07–1.18) 0.13 EMP62E -Monocyte Conjugates, MFI (IQR) 1.17 (1.02–1.19) 1.31 (1.22–1.56) 0.0005 EMP62E -Neutrophil Conjugates, MFI (IQR) 1.47 (1.21–2.01) 1.94 (1.57–2.52) 0.10
HIV Infection, Antiretroviral Therapy, and CD4+Cell Count Distributions in African Populations