Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins Academic Article uri icon

Overview

MeSH Major

  • Atherosclerosis
  • Lipoproteins, LDL
  • Macrophages

abstract

  • A critical event in atherogenesis is the interaction of macrophages with subendothelial lipoproteins. Although most studies model this interaction by incubating macrophages with monomeric lipoproteins, macrophages in vivo encounter lipoproteins that are aggregated. The physical features of the lipoproteins require distinctive mechanisms for their uptake. We show that macrophages create an extracellular, acidic, hydrolytic compartment to carry out digestion of aggregated low-density lipoproteins. We demonstrate delivery of lysosomal contents to these specialized compartments and their acidification by vacuolar ATPase, enabling aggregate catabolism by lysosomal acid hydrolases. We observe transient sealing of portions of the compartments, allowing formation of an "extracellular" proton gradient. An increase in free cholesterol is observed in aggregates contained in these compartments. Thus, cholesteryl ester hydrolysis can occur extracellularly in a specialized compartment, a lysosomal synapse, during the interaction of macrophages with aggregated low-density lipoprotein. A detailed understanding of these processes is essential for developing strategies to prevent atherosclerosis.

publication date

  • December 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2785736

Digital Object Identifier (DOI)

  • 10.1091/mbc.E09-07-0559

PubMed ID

  • 19812252

Additional Document Info

start page

  • 4932

end page

  • 40

volume

  • 20

number

  • 23