The unstirred water layer as a site of control of apolipoprotein B secretion.

Apolipoprotein B-100 (apoB) is a constituent of low density lipoproteins that has been implicated in the development of coronary artery disease (Editorial (1988) Lancet 1, 1141-1142). It is produced primarily in the liver, but mechanisms of secretory control are unclear. We examined the possibility that rapid reuptake of newly secreted lipoproteins regulates the net output of apoB by cultured liver cells. Polyclonal blocking antibodies to the low density lipoprotein receptor markedly increased apoB output, and varying the width of the unstirred water layer around the cells also changed apoB output, consistent with local reuptake. Labeled apoB added to the bulk fluid phase of the incubation media was not detectably taken up, implying that re-uptake is predominantly local. We conclude that a major site of apoB secretory control resides in the unstirred water layer, external to the cell. Because many cells secrete products for which they possess receptors, local re-uptake from the unstirred water layer may be a general mechanism for secretory control.