Receptor-independent fluid-phase pinocytosis mechanisms for ... : Current Opinion in Lipidology (original) (raw)

Atherosclerosis: cell biology and lipoproteins: Edited by Petri T. Kovanen and Andrew Newby

Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam cell formation with native low-density lipoprotein particles

Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA

Correspondence to Dr Howard S. Kruth, Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 5N113, 10 Center Drive MSC-1422, Bethesda, MD 20892-1422, USA Tel: +1 301 496 4826; fax: +1 301 402 4359; e-mail: [email protected]

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Abstract

Purpose of review

Because early findings indicated that native low-density lipoprotein (LDL) did not substantially increase macrophage cholesterol content during in-vitro incubations, investigators presumed that LDL must be modified in some way to trigger its uptake by the macrophage. The purpose of this review is to discuss recent findings showing that native unmodified LDL can induce massive macrophage cholesterol accumulation mimicking macrophage foam cell formation that occurs within atherosclerotic plaques.

Recent findings

Macrophages that show high rates of fluid-phase pinocytosis also show similar high rates of uptake of native unmodified LDL through nonreceptor mediated uptake within both macropinosomes and micropinosomes. Nonsaturable fluid-phase uptake of LDL by macrophages converts the macrophages into foam cells. Different macrophage phenotypes demonstrate either constitutive fluid-phase pinocytosis or inducible fluid-phase pinocytosis. Fluid-phase pinocytosis has been demonstrated by macrophages within mouse atherosclerotic plaques indicating that this pathway contributes to plaque macrophage cholesterol accumulation.

Summary

Contrary to what has been believed previously, macrophages can take up large amounts of native unmodified LDL by receptor-independent, fluid-phase pinocytosis converting these macrophages into foam cells. Thus, targeting macrophage fluid-phase pinocytosis should be considered when investigating strategies to limit macrophage cholesterol accumulation in atherosclerotic plaques.