alpha 2-macroglobulin stimulation of protein tyrosine phosphorylation in macrophages via the mannose receptor for Fc gamma receptor-mediated phagocytosis activation.
Macrophage phagocytic activity has previously been shown to be increased by binding of modified alpha 2-macroglobulin (alpha 2M) with mannose residues at termini of sugar chains to mannose receptors on macrophages, with a subsequent increase in the number of Fc gamma receptors at the cell surface. In the present study, an examination was made of the association of protein tyrosine kinase with the increase in number of Fc gamma receptors following binding of modified alpha 2M to mannose receptors. The phagocytosis of IgG-opsonized sheep red blood cells through the action of the Fc gamma receptor by modified alpha 2M was inhibited by mannose and herbimycin A and slightly so by genistein. The mannose receptor would thus appear to be associated with tyrosine kinase activity. By Western blotting, tyrosine phosphorylated proteins with molecular weights of 32000, 34000, 36000, 65000, 85000 and 110000 appeared or increased upon treating macrophages with modified alpha 2M. The degree of tyrosine phosphorylated proteins was the same for control macrophages following incubation in the presence of mannose and herbimycin A. Genistein treatment affected only tyrosine phosphorylated proteins of 65000 and 110000. The binding of modified alpha 2M to mannose receptors was demonstrated by the inducement of tyrosine kinase activation that was sensitive to herbimycin A, followed by an increase in Fc gamma receptors and consequently greater phagocytosis.
Murai
M
M
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Aramaki
Y
Y
Tsuchiya
S
S
D000818:Animals; D018929:Cell Culture Techniques; D037181:Lectins, C-Type; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D000511:alpha-Macroglobulins; D011505:Protein-Tyrosine Kinases