Regulation of Signal Transduction by the Fcγ Receptor Family Members and Their Involvement in Autoimmunity

2001 ◽  
pp. 1-29 ◽  
Author(s):  
K.M. Coggeshall
Keyword(s):  
Signal Transduction ◽  
Family Members ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Receptor Family

scholarly journals Insertion of cytoplasmic tyrosine sequences into the nonphagocytic receptor Fc gamma RIIB establishes phagocytic function

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2072-2080 ◽  
Author(s):  
ZK Indik ◽  
XQ Pan ◽  
MM Huang ◽  
SE McKenzie ◽  
AI Levinson ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Receptor Activation ◽  
Molecular Structures ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Hematopoietic Lineage ◽  
Receptor Isoforms ◽  
Low Levels ◽  
Tyrphostin 23 ◽  
Receptor Family

Abstract Receptors for the Fc domain of IgG on cells of hematopoietic lineage perform important functions, including stimulation of the ingestion of IgG-coated cells. In examining the function of Fc gamma receptor isoforms by transfection into COS-1 cells, we have observed that Fc gamma RIIA induces the binding and phagocytosis of IgG-sensitized RBCs (EA) and that transfected COS-1 cells can serve as a model for examining the molecular structures involved in mediating a phagocytic signal. We now report that COS-1 cell transfectants expressing the isoforms Fc gamma RIIB1 and Fc gamma RIIB2 and a Fc gamma RIIA mutant without a cytoplasmic tail efficiently bind EA but do not mediate their phagocytosis. Furthermore, wild-type Fc gamma RIIA, but not Fc gamma RIIB1 or Fc gamma RBII2, was phosphorylated on tyrosine upon receptor activation. Tyrphostin 23, which alters tyrosine kinase activity, inhibited the phagocytosis of EA and reduced the phosphorylation of Fc gamma RIIA on tyrosine. Fc gamma RIIB1 and Fc gamma RIIB2 contain one copy of the cytoplasmic sequence YXXL/I implicated in signal transduction, whereas Fc gamma RIIA contains two copies. We therefore inserted YXXL/I sequences at different sites in Fc gamma RIIB2. Low levels of phagocytosis were observed in a Fc gamma RIIB2 mutant bearing the Fc gamma RIIA sequence YMTL and higher levels of phagocytosis were observed in a second Fc gamma RIIB2 mutant that contained both the upstream YMTL and an additional downstream tyrosine-containing motif. Activation of this mutant receptor also induced receptor tyrosine phosphorylation. Thus, these studies indicate that both the number and placement of YXXL sequences in the cytoplasmic domain of the Fc gamma RII receptor family affect both receptor tyrosine phosphorylation and phagocytic competence.

scholarly journals Insertion of cytoplasmic tyrosine sequences into the nonphagocytic receptor Fc gamma RIIB establishes phagocytic function

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2072-2080 ◽  
Author(s):  
ZK Indik ◽  
XQ Pan ◽  
MM Huang ◽  
SE McKenzie ◽  
AI Levinson ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Receptor Activation ◽  
Molecular Structures ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Hematopoietic Lineage ◽  
Receptor Isoforms ◽  
Low Levels ◽  
Tyrphostin 23 ◽  
Receptor Family

Receptors for the Fc domain of IgG on cells of hematopoietic lineage perform important functions, including stimulation of the ingestion of IgG-coated cells. In examining the function of Fc gamma receptor isoforms by transfection into COS-1 cells, we have observed that Fc gamma RIIA induces the binding and phagocytosis of IgG-sensitized RBCs (EA) and that transfected COS-1 cells can serve as a model for examining the molecular structures involved in mediating a phagocytic signal. We now report that COS-1 cell transfectants expressing the isoforms Fc gamma RIIB1 and Fc gamma RIIB2 and a Fc gamma RIIA mutant without a cytoplasmic tail efficiently bind EA but do not mediate their phagocytosis. Furthermore, wild-type Fc gamma RIIA, but not Fc gamma RIIB1 or Fc gamma RBII2, was phosphorylated on tyrosine upon receptor activation. Tyrphostin 23, which alters tyrosine kinase activity, inhibited the phagocytosis of EA and reduced the phosphorylation of Fc gamma RIIA on tyrosine. Fc gamma RIIB1 and Fc gamma RIIB2 contain one copy of the cytoplasmic sequence YXXL/I implicated in signal transduction, whereas Fc gamma RIIA contains two copies. We therefore inserted YXXL/I sequences at different sites in Fc gamma RIIB2. Low levels of phagocytosis were observed in a Fc gamma RIIB2 mutant bearing the Fc gamma RIIA sequence YMTL and higher levels of phagocytosis were observed in a second Fc gamma RIIB2 mutant that contained both the upstream YMTL and an additional downstream tyrosine-containing motif. Activation of this mutant receptor also induced receptor tyrosine phosphorylation. Thus, these studies indicate that both the number and placement of YXXL sequences in the cytoplasmic domain of the Fc gamma RII receptor family affect both receptor tyrosine phosphorylation and phagocytic competence.

scholarly journals Prominent Indomethacin-Induced Enteropathy in Fcgriib Defi-cient lupus Mice: An Impact of Macrophage Responses and Immune Deposition in Gut

2021 ◽  
Vol 22 (3) ◽  
pp. 1377
Author(s):  
Thansita Bhunyakarnjanarat ◽  
Kanyarat Udompornpitak ◽  
Wilasinee Saisorn ◽  
Bhumdhanin Chantraprapawat ◽  
Peerapat Visitchanakun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
High Dose ◽  
Flux Analysis ◽  
Wild Type ◽  
Fc Gamma Receptor ◽  
Serum Cytokines ◽  
Extracellular Flux ◽  
Gamma Receptor ◽  
Gut Leakage ◽  
Gastrointestinal Permeability

A high dose of NSAIDs, a common analgesic, might induce lupus activity through several NSAIDs adverse effects including gastrointestinal permeability defect (gut leakage) and endotoxemia. Indomethacin (25 mg/day) was orally administered for 7 days in 24-wk-old Fc gamma receptor IIb deficient (FcgRIIb-/-) mice, an asymptomatic lupus model (increased anti-dsDNA without lupus nephritis), and age-matched wild-type (WT) mice. Severity of indomethacin-induced enteropathy in FcgRIIb-/- mice was higher than WT mice as demonstrated by survival analysis, intestinal injury (histology, immune-deposition, and intestinal cytokines), gut leakage (FITC-dextran assay and endotoxemia), serum cytokines, and lupus characteristics (anti-dsDNA, renal injury, and proteinuria). Prominent responses of FcgRIIb-/- macrophages toward lipopolysaccharide (LPS) compared to WT cells due to the expression of only activating-FcgRs without inhibitory-FcgRIIb were demonstrated. Extracellular flux analysis indicated the greater mitochondria activity (increased respiratory capacity and respiratory reserve) in FcgRIIb-/- macrophages with a concordant decrease in glycolysis activity when compared to WT cells. In conclusion, gut leakage-induced endotoxemia is more severe in indomethacin-administered FcgRIIb-/- mice than WT, possibly due to the enhanced indomethacin toxicity from lupus-induced intestinal immune-deposition. Due to a lack of inhibitory-FcgRIIb expression, mitochondrial function, and cytokine production of FcgRIIb-/- macrophages were more prominent than WT cells. Hence, lupus disease-activation from NSAIDs-enteropathy-induced gut leakage is possible.

scholarly journals Murine autoimmune hemolytic anemia resulting from Fc gamma receptor- mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2960-2964 ◽  
Author(s):  
T Berney ◽  
T Shibata ◽  
R Merino ◽  
Y Chicheportiche ◽  
V Kindler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Colony Stimulating Factor ◽  
Fc Gamma Receptor ◽  
Interleukin 3 ◽  
Gamma Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor- mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM-CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia.

Identification of Toll-like receptor family members in Oncomelania hupensis and their role in defense against Schistosoma japonicum

Acta Tropica ◽  
2018 ◽  
Vol 181 ◽  
pp. 69-78 ◽  
Author(s):  
Qin Ping Zhao ◽  
Qian Gao ◽  
Yan Zhang ◽  
Yan Wei Li ◽  
Wen Ling Huang ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Family Members ◽  
Toll Like Receptor ◽  
Oncomelania Hupensis ◽  
Receptor Family
Sign in / Sign up

Export Citation Format

Share Document