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Electroimmunoassays ("rocket" electrophoresis) are described for human serum apolipoprotein A and its constitutive A-I and A-II polypeptides. Purified lipoprotein A, A-I, and A-II were used to prepare monospecific antisera and to standardize assays. These specific, rapid (5-8 h), precise (the within-and between-assay coefficients of variations are 5 and 7%, respectively), and accurate (by gravimetry) assays are applicable to measurement of these polypeptides in whole serum and in various density classes of lipoproteins. Comparable results are obtained with intact and delipidized lipoproteins. Results correlated well with those obtained by radial immunodiffusion or radioimmunoassay. However, the present procedure is more rapid than the former and simpler than the latter immunoassay. Concentrations of A-I and A-II in the serum of normal men and women were similar (143 +/- 24 and 146 +/- 78 mg/dl, respectively, for A-I and 78 +/- 17 and 83 +/- 25 mg/dl for A-II). Subjects with type lla, llb, and IV hyperlipoproteinemias had similar concentrations of both polypeptides, while patients with type I disease, lecithin:cholesterol acyltransferase deficiency and LP-A deficiency had lowest concentrations of A-I (0.3-30 mg/dl) and A-II (11-20 mg/dl). The molar ratio of A-I/A-II in the serum and high-density lipoproteins was close to unity.

The ultrastructural features of peripheral blood monocyte margination, migration, and aortic intimal accumulation have been described in the normo- and mildly hypercholesterolemic baboon. Intimal monocyte-macrophage recruitment over fatty streaks and fibro-fatty plaques was enhanced by dietary cholesterol-fat supplementation, resulting in an 8-fold increase in monocyte-macrophages and macrophage-derived foam cells in the subendothelial space. Margination or attachment observed over both plaques and normal areas was not associated with morphologic evidence of endothelial injury. Migration through continuous aortic endothelium was principally between endothelial cells via junctions. Transitional sequences from the typical morphology of the blood monocyte to the lipid-containing macrophage or foam cell were discerned. The intimal accumulation of monocytes and macrophages reinforces our view of atherosclerosis as an inflammatory process, in which monocyte attachment is likely to reflect changes in the endothelial surface-membrane complex and surface charge, while migration to and accumulation in the SES may result from one or more chemoattractants originating in the intima or media.

This article has addressed the roles of the monocyte-macrophage in atherogenesis and factors influencing monocyte recruitment to the intima. The diversity of the secretory products of the macrophage and their putative participatory roles in pathogenesis have been reviewed and discussed. Additionally, we have presented summary data on the monocyte chemoattractant peptide SMC-CF and on the differentiation of the monocyte-derived foam cell. Discussion has centered on the concept of atherosclerosis as an inflammatory process.

In this brief review, we have addressed the roles of the monocyte-macrophage in atherogenesis, with emphasis on the recruitment to the arterial wall. We have presented summary data on the SMC-derived chemoattractant protein and also on the temporal evolution of monocyte-derived macrophages into cholesteryl ester-rich foam cells. The concept of atheroma as an inflammatory process has also been discussed.

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