Macrophages play an important role in atherogenesis and have been repo
rted within the intima at lesion-prone sites in normocholesterolemic a
nimals as well as infants and children. The objective of this study wa
s to determine the spatial distribution of intimal white blood cells (
WBC) in the normal rabbit aorta and the association of intimal WBC wit
h replicating endothelial cells and sites of increased I-125-LDL perme
ability. Intimal WBC and macrophages were identified en face on whole
aortic tissue and on Hautchen preparations based on their morphology,
ingestion of exogenous horseradish peroxidase, non-specific esterase a
ctivity, and labeling with a monoclonal antibody for rabbit macrophage
s (RAM11). WBC were primarily located in the lesion-prone flow divider
regions of the large abdominal branch arteries. Using [H-3]thymidine
autoradiography to determine cell proliferation, 4.4% of the WBC and 0
.12% of the endothelial cells were labeled on the Hautchen preparation
s. The distribution of replicating endothelial cells was not localized
to the arterial orifices and was not correlated with the distribution
of intimal WBC. Intimal WBC were, however, spatially correlated with
the distribution of I-125-LDL permeable sites about the celiac artery
orifice and were directly associated with 31% of the LDL permeable spo
ts. Moreover, mitotic endothelial cells accounted for only 8% of the t
otal number of LDL permeable sites. The presence of intimal WBC at les
ion-prone sites in the normocholesterolemic rabbit suggests that these
cells may be important in the initiation of atherosclerotic lesions.