PERIPHERAL-BLOOD MONONUCLEAR PHAGOCYTE SUBPOPULATIONS AS CELLULAR MARKERS IN HYPERCHOLESTEROLEMIA

Mononuclear phagocytes play a major role in the development of vascula r lesions in atherogenesis. The goal of our study was to characterize circulating blood monocyte subpopulations as potential cellular marker s of systemic immunological abnormalities in hypercholesterolemia. In normal subjects, three-parameter immunophenotyping of whole blood reve aled that 61.3+/-6.0% of monocytes showed ''bright'' expression of the lipopolysaccharide receptor (LPSR: CD14) and Fc gamma receptor I(RI: CD64) without expression of Fc gamma-RIII (CD 16). Other monocyte subs ets (populations 2, 3, 4, and 5) were characterized by the simultaneou s expression of both Fc gamma-R's (25.6+/-5.0%), isolated expression o f Fc gamma-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 po pulation of CD14(bright)D64(+)CD16(-) monocytes by additional expressi on of neural cell adhesion molecule (N-CAM: CD56). In a group of hyper cholesterolemic pa tients (n=19), high density lipoprotein cholesterol levels were negatively correlated to the population size of CD64(-)CD 16(+) monocytes. In both healthy subjects (n=55) and hypercholesterole mic 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 pe ripheral 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 nuclear phagocyte subpopulations may play a role in the p athogenesis of atherosclerosis.