Factors regulating the activities of the low density lipoprotein receptor and the scavenger receptor on human monocyte-macrophages.

Abstract

Improved techniques of cell isolation resulted in 90 to 100 million monocytes from a single donor. Addition of low density lipoprotein (LDL) to to cultures of these cells resulted in the down regulation of LDL receptor activity. Addition of malondialdehyde-altered LDL. which enters the cell through a receptor for negatively charged proteins (the scavenger receptor), produced an even greater down regulation of the LDL receptor, indicating that both receptors are present on the same cell. Within hours of adherence of the cells, there was a dramatic decrease in the activity of both receptors. LDL receptor activity was highest during the first week in culture and then declined, despite the maintenance of a constant LDL concentration in the medium. Scavenger receptor activity surpassed LDL receptor activity by the 6th day and was maximally expressed during the second week. Increasing cell density resulted in a slight increase in the activity of the LDL receptor and a dramatic increase in scavenger receptor activity. Insulin had no significant effect on either receptor. Removing serum from the culture medium for 48 hr resulted in a 3.5-fold increase in LDL receptor activity and a 2-fold decrease in scavenger receptor activity. Twenty-four hr after the cells were re-exposed to serum, the activities of both receptors essentially returned to base line. Heat-inactivation of serum was associated with an increased cholesteryl ester content of the cells and depressed receptor activities. Scavenger receptor activity appears related to the maturation of monocytes into macrophages and is promoted by increasing cell density and serum factors that are heat labile.