Evidence from diverse sources has implicated a central role of apolipoprotein AI (apo AI), the most abundant protein of plasma high‐density lipoproteins, in the transport of cholesterol from peripheral tissues to the liver (reverse cholesterol transport). Particles containing only apo AI appear to be more effective as cholesterol acceptors in tissue culture than do particles which also contain apo AII The apo AI‐containing lipoproteins of plasma have been extensively studied, but there is less information on those in tissue fluids, to which most peripheral cells are exposed. In the present study the heterogeneity of apo AI‐containing particles in human peripheral lymph, collected from the dorsum of the foot, has been examined by starch block electrophoresis, exclusion chromatography and immunoelectrophoresis.

The apo AI‐containing particles of lymph were found to be more variable in both electrophoretic mobility and size than those of plasma from the same subjects. Of particular interest was a subpopulation which migrated on electrophoresis with the same mobility as alpha‐2‐macroglobulin. This fraction accounted for approximately 7% (range: 4–12%; n= 5) of lymph apo AI, contained no immunodetectable apo AII, and by exclusion chromatography was composed of particles the size of, or smaller than, albumin. Such physicochemical properties suggest that these alpha‐2 migrating particles may function as the principal primary acceptors of cell cholesterol in the extracellular matrix of human peripheral tissues. By isoelectric focusing, lymph apo AI was found to contain a higher proportion of more negatively charged isoforms than the apo AI of plasma.