Peripheral blood mononuclear phagocyte subpopulations as cellular markers in hypercholesterolemia

Abstract

Mononuclear phagocytes play a major role in the development of vascular lesions in atherogenesis. The goal of our study was to characterize circulating blood monocyte subpopulations as potential cellular markers of systemic immunological abnormalities in hypercholesterolemia. In normal subjects, three parameter immunophenotyping of whole blood revealed that 61.3±6.0% of monocytes showed 'bright' expression of the lipopolysaccharide receptor (LPSR: CD14) and Fcγ receptor I (RI: CD64) without expression of Fcγ-RIII (CD16). Other monocyte subsets (populations 2, 3, 4, and 5) were characterized by the simultaneous expression of both Fcγ-R's (25.6±5.0%), isolated expression of Fcγ-RIII (9.4±1.7%), or high expression of CD33 (3.7±1.1%) with only dim expression of CD14, respectively. The smallest subset of monocytes (population 5: 2.1±0.8%) differed from the predominant population of CD14(bright)CD64+CD16monocytes by additional expression of neural cell adhesion molecule (N-CAM: CD56). In a group of hypercholesterolemic patients (n=19), high density lipoprotein cholesterol levels were negatively correlated to the population size of CD64-CD16+ monocytes. In both healthy subjects (n=55) and hypercholesterolemic patients, the rare apolipoprotein E3/E4 and E4/E4 phenotypes were associated with a tendency toward a larger population of CD64-CD16+ monocytes. Expression of the variant activation antigen CD45RA by peripheral blood mononuclear phagocytes showed a positive correlation to plasma levels of the atherogenic lipoproteins low density lipoprotein and lipoprotein(a). These data suggest that systemic abnormalities in mononuclear phagocyte subpopulations may play a role in the pathogenesis of atherosclerosis.