Induction of macrophage growth by phagocytic stimuli via scavenger receptor.

Abstract

Scavenger receptors on macrophages were recently discovered and molecularly identified. Although the roles of the scavenger receptors in phagocytic function of macrophage were well-characterized, it might affect on many macrophage functions other than phagocytosis. Macrophage growth is known to be induced by protein factors, namely, macrophage colony-stimulating factor (CSF) and granulocyte/macrophage CSF. On the other hand, we previously reported that phagocytic stimuli of dead cells or cell membrane component induce the growth of macrophages. Therefore, the possibility was raised that macrophage growth could also be induced by ligands for scavenger receptors such as chemically modified lipoproteins or advanced glycation end products (AGE) of proteins. Actually, when murine peritoneal exudate macrophages were cultured with acetylated LDL, oxidized LDL, or AGE-BSA, significant growth was induced. These in vitro data revealed a new function of ligands of scavenger receptors as effective inducers of macrophage growth. Capacity of AGE-BSA to induce macrophage growth was blocked when the cells were cultured with antibody to GM-CSF. Moreover, it was confirmed that AGE actually induced production of GM-CSF in macrophages. Therefore, it is suggested that endogenous production of GM-CSF is implicated in the growth-stimulating activity of the ligands of scavenger receptors.