Role of N-terminal domain of histidine-rich glycoprotein in modulation of macrophage Fc gamma receptor-mediated phagocytosis.
A brief exposure of murine peritoneal inflammatory macrophages to plasma histidine-rich glycoprotein (HRG; 77,000-81,000 MW) for 1-2 hr increased Fc gamma receptor (Fc gamma R) expression and phagocytic function in these cells. However, a continual culture of the cells without the presence of HRG for the next 18-48 hr resulted in down-regulation of Fc gamma R expression and phagocytic function. Similarly, HRG decreased Fc gamma RII expression in less differentiated human THP-1 monocytic cells during treatment for 18 hr, as determined by cellular ELISA and metabolic labelling. The molecular mechanism by which HRG regulates Fc gamma R expression is unknown. However, at a relatively high concentration (> 1 microgram/ml), HRG altered the cellular metabolism by increasing cellular protein synthesis but reducing protein secretion. These observations suggest a likely mechanism for the HRG-mediated reduction of Fc gamma R expression. A degraded HRG (40,000 MW) which possessed an identical N-terminal sequence as that of the native HRG was capable of decreasing macrophage Fc gamma R expression and phagocytosis. The results indicate that the functional domain of HRG responsible for binding to macrophages is localized to the N-terminal half.
Chang
N S
NS
Guthrie Research Institute, Laboratory of Molecular Immunology, Guthrie Medical Center, Sayre, Pennsylvania 18840.
Leu
R W
RW
Anderson
J K
JK
Mole
J E
JE
D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis / Q000187:drug effects*; D011506:Proteins / Q000737:chemistry / Q000187:drug effects / Q000494:pharmacology*; D017452:Receptors, IgG / Q000032:analysis / Q000187:drug effects*; D000099053:Histidine-Rich Glycoprotein
D006023:Glycoproteins; D011506:Proteins; D017452:Receptors, IgG; D000099053:Histidine-Rich Glycoprotein