Faculty Collaboration Database

Regulated expression of CD36 during monocyte-to-macrophage differentiation: potential role of CD36 in foam cell formation. Blood 1996 Mar 01;87(5):2020-8

Date

03/01/1996

Pubmed ID

8634453

Scopus ID

2-s2.0-0000685254 (requires institutional sign-in at Scopus site)   239 Citations

Abstract

CD36 is an 88-kD integral membrane glycoprotein expressed on monocytes, platelets, and certain microvascular endothelium serving distinct cellular functions both as an adhesive receptor for thrombospondin, collagen, and Plasmodium falciparum-infected erythrocytes, and as a scavenger receptor for oxidized low-density lipoprotein and apoptotic neutrophils. In this study, we examined the expression of CD36 during in vitro differentiation of peripheral blood monocytes into culture-derived macrophages. Steady-state mRNA levels of CD36 showed a transient eightfold increase during monocyte-to-macrophage differentiation, peaking at the early macrophage stage (days 3 or 4 in culture), following a gradual decrease back to baseline levels by the mature macrophage stage (days 7 or 8 in culture). Immunoblotting with monoclonal antibodies to CD36 supported this transient, yet significant (8- to 10-fold) increase in total protein levels of CD36. The increased CD36 protein was observed at the plasma membrane, whereas an intracellular pool of CD36 was also detected from day 2 to day 6 in culture through indirect immunofluorescence. A concomitant twofold increase in the cells' ability to bind 125I-thrombospondin at the early macrophage stage (day 4) verified the functional competency of the plasma membrane localized CD36, and supported the presence of an intracellular pool of CD36. The in vitro differentiated macrophages as well as alveolar macrophages remained responsive to macrophage colony-stimulating factor (M-CSF), a known transcriptional regulator of monocyte CD36. The M-CSF-induced macrophages resulted in enhanced foam cell formation, which was inhibitable with monoclonal antibodies to CD36. Thus, the transient expression of CD36 during monocyte-to-macrophage differentiation, and the ability of M-CSF to maintain macrophage CD36 at elevated levels, may serve as a critical process in dictating the functional activity of CD36 during inflammatory responses and atherogenesis.

Author List

Huh HY, Pearce SF, Yesner LM, Schindler JL, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
CD36 Antigens
Cell Differentiation
Cell Membrane
Cells, Cultured
Foam Cells
Gene Expression Regulation
Humans
Intracellular Fluid
Lipoproteins, LDL
Macrophage Colony-Stimulating Factor
Macrophages
Macrophages, Alveolar
Mice
Monocytes
RNA, Messenger