Premium
Galectin‐3/MAC‐2, Ras and PI3K activate complement receptor‐3 and scavenger receptor‐AI/II mediated myelin phagocytosis in microglia
Author(s) -
Rotshenker Shlomo,
Reichert Fanny,
Gitik Miri,
Haklai Ronit,
EladSfadia Galit,
Kloog Yoel
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20713
Subject(s) - phagocytosis , microglia , biology , pi3k/akt/mtor pathway , microbiology and biotechnology , scavenger receptor , receptor , myelin , complement receptor , immunology , complement system , biochemistry , neuroscience , signal transduction , antibody , inflammation , central nervous system , lipoprotein , cholesterol
Abstract The removal of degenerated myelin is essential for repair in Wallerian degeneration that follows traumatic injury to axons and in autoimmune demyelinating diseases (e.g., multiple sclerosis). Microglia can remove degenerated myelin through phosphatidylinositol‐3‐kinase (PI3K)‐dependent phagocytosis mediated by complement receptor‐3 (CR3/MAC‐1) and scavenger receptor‐AI/II (SRAI/II). Paradoxically, these receptors are expressed in microglia after injury but myelin is not phagocytosed. Additionally, Galectin‐3/MAC‐2 is expressed in microglia that phagocytose but not in microglia that do not phagocytose, suggesting that Galectin‐3/MAC‐2 is instrumental in activating phagocytosis. S ‐trans, trans‐farnesylthiosalicylic (FTS), which inhibits Galectin‐3/MAC‐2 dependent activation of PI3K through Ras, inhibited phagocytosis. K‐Ras‐GTP levels and PI3K activity increased during normal phagocytosis and decreased during FTS‐inhibited phagocytosis. Galectin‐3/MAC‐2, which binds and stabilizes active Ras, coimmunoprecipitated with Ras and levels of the coimmunoprecipitate increased during normal phagocytosis. A role for Galectin‐3/MAC‐2 dependent activation of PI3K through Ras, mostly K‐Ras, is thus suggested. An explanation may thus be offered for deficient phagocytosis by microglia that express CR3/MAC‐1 and SRAI/II without Galectin‐3/MAC‐2 and efficient phagocytosis when CR3/MAC‐1 and SRAI/II are co‐expressed with Galectin‐3/MAC‐2. © 2008 Wiley‐Liss, Inc.