scholarly journals Enhancement of Splenic-Macrophage Fcγ Receptor Expression by Treatment with Estrogens

2001 ◽  
Vol 8 (4) ◽  
pp. 806-810 ◽  
Author(s):  
F. Gomez ◽  
P. Ruiz ◽  
J. A. Bernal ◽  
M. Escobar ◽  
A. Garcia-Egido ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Fcγ Receptors ◽  
Dopaminergic Drugs ◽  
Splenic Macrophage ◽  
Splenic Macrophages ◽  
17Β Estradiol

ABSTRACT Splenic-macrophage Fcγ receptors (FcγRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcγR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcγR expression. Previous data indicate that estradiol increases macrophage FcγR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcγR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcγRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17β-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcγR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcγR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcγR1 and -2 more than that of FcγR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcγR expression.

scholarly journals Effects of Androgen Treatment on Expression of Macrophage Fcγ Receptors

2000 ◽  
Vol 7 (4) ◽  
pp. 682-686 ◽  
Author(s):  
F. Gomez ◽  
P. Ruiz ◽  
R. Lopez ◽  
C. Rivera ◽  
S. Romero ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Immune Disorders ◽  
Fcγ Receptors ◽  
Splenic Macrophage ◽  
Androgen Treatment ◽  
Splenic Macrophages ◽  
Guinea Pig Model

ABSTRACT Macrophage Fcγ receptors (FcγRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcγR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcγR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcγRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage FcγR cell surface expression. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcγR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcγR1,2 more than that of FcγR2. Antiandrogens did not significantly alter macrophage FcγR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcγR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcγR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

2008 ◽  
Vol 295 (6) ◽  
pp. F1864-F1870 ◽  
Author(s):  
Glenn T. Nagami ◽  
Jenny A. Chang ◽  
Megan E. Plato ◽  
Rafael Santamaria
Keyword(s):  
Cell Surface ◽  
Proximal Tubule ◽  
Surface Expression ◽  
Low Ph ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Ang Ii ◽  
Proximal Tubule Cells ◽  
Acid Loading

The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH4Cl acid loading in vivo on renal cortical type 1 ANG II (AT1) receptor expression, the effect of low pH on AT1 receptor expression in a proximal tubule cells in culture, and their response to ANG II. A short-term (18 h) NH4Cl load in vivo resulted in increased renal cortical AT1 receptor mRNA expression and increased brush-border membrane AT1 receptor protein expression levels. Changing the cell culture pH from 7.4 to 7.0 for at least 2 h increased cell surface expression of AT1 receptors and enhanced the stimulatory effect of ANG II on ammonia production rates. This increased ammoniagenic response to ANG II and the early enhancement of cell surface expression induced by exposure of the cultured proximal tubule cells to pH 7.0 were prevented by treatment with colchicine. These results suggest that, after acid challenges, the enhanced ammoniagenic response of the proximal tubule to ANG II is, in part, mediated by increased AT1 receptor cell surface expression and that the enhancement of receptor expression plays an important role in the early response of the proximal tubule to acid challenges.

scholarly journals Estrogens Augment Cell Surface TLR4 Expression on Murine Macrophages and Regulate Sepsis Susceptibility in Vivo

Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3877-3884 ◽  
Author(s):  
Jennifer A. Rettew ◽  
Yvette M. Huet ◽  
Ian Marriott
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Toll Like Receptor ◽  
Lipopolysaccharide Binding Protein ◽  
Toll Like Receptor 4 ◽  
17Β Estradiol ◽  
Lipopolysaccharide Binding

Gender-based differences exist in infectious disease susceptibility. In general, females generate more robust and potentially protective humoral and cell-mediated immune responses after antigenic challenge than their male counterparts. Furthermore, evidence is accumulating that sex may also influence the early perception of microbial challenges and the generation of inflammatory immune responses such as sepsis. These differences have previously been attributed to the actions of reproductive hormones. Whereas androgens have been shown to suppress acute host immune responses to bacterial endotoxin challenge, estrogens have been found to promote increased resistance to bacterial infections. However, the mechanisms by which estrogens exert immunoprotective effects have not been established. In this study, we investigated the in vivo effects of 17β-estradiol on endotoxin susceptibility in mice. Importantly, we have examined the actions of this female reproductive hormone on the expression of pattern recognition receptors that recognize bacterial endotoxin by key innate immune sentinel cells. We show that removal of endogenous estrogens decreases both pro- and antiinflammatory cytokine production, with a concomitant reduction in circulating levels of lipopolysaccharide-binding protein and cell surface expression of Toll-like receptor 4 on murine macrophages. Exogenous in vivo replacement of 17β-estradiol, but not progesterone, significantly elevates sera lipopolysaccharide-binding protein levels and cell surface expression of Toll-like receptor 4 and CD14 on macrophages. Furthermore, this effect corresponds with significantly higher inflammatory cytokine levels after in vivo lipopolysaccharide challenge and a marked increase in endotoxin-associated morbidity. Taken together, these data provide a potential mechanism underlying the immunoenhancing effects of estrogens.

Impact of β2 integrin deficiency on mouse natural killer cell development and function

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2874-2882 ◽  
Author(s):  
Karine Crozat ◽  
Céline Eidenschenk ◽  
Baptiste N. Jaeger ◽  
Philippe Krebs ◽  
Sophie Guia ◽  
...  
Keyword(s):  
Cell Surface ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Surface Expression ◽  
Cell Maturation ◽  
Cell Surface Expression ◽  
Mcmv Infection ◽  
Β2 Integrin

Abstract Natural killer (NK) cells are innate immune cells that express members of the leukocyte β2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A → T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that β2 integrin–deficient NK cells have a hyporesponsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit+ cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, β2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses.

scholarly journals Functional Analysis of the Murine Cytomegalovirus Chemokine Receptor Homologue M33: Ablation of Constitutive Signaling Is Associated with an Attenuated Phenotype In Vivo

2007 ◽  
Vol 82 (4) ◽  
pp. 1884-1898 ◽  
Author(s):  
Ruth Case ◽  
Emma Sharp ◽  
Tau Benned-Jensen ◽  
Mette M. Rosenkilde ◽  
Nicholas Davis-Poynter ◽  
...  
Keyword(s):  
Cell Surface ◽  
Salivary Glands ◽  
Surface Expression ◽  
Receptor Activation ◽  
Murine Cytomegalovirus ◽  
Cell Surface Expression ◽  
Transmembrane Receptors ◽  
C Terminus ◽  
The Impact

ABSTRACT The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous studies have demonstrated that M33 is important for MCMV dissemination to or replication within the salivary glands. In this study, we probed N- and C-terminal regions of M33 as well as known 7TMR signature motifs in transmembrane (TM) II and TM III to determine the impact on cell surface expression, constitutive signaling, and in vivo phenotype. The region between amino acids R340 and A353 of the C terminus was found to be important for CREB- and NFAT-mediated signaling, although not essential for phosphatidylinositol turnover. Tagging or truncation of the N terminus of M33 resulted in loss of cell surface expression. Within TM II, an F79D mutation abolished constitutive signaling, demonstrating a role, as in other cellular and viral 7TMR, of TM II in receptor activation. In TM III, the arginine (but not the asparagine) residue of the NRY motif (the counterpart of the common DRY motif in cellular 7TMR) was found to be essential for constitutive signaling. Selected mutations incorporated into recombinant MCMV showed that disruption of constitutive signaling for a viral 7TMR homologue resulted in a reduced capacity to disseminate to or replicate in the salivary glands. In addition, HCMV UL33 was found to partially compensate for the lack of M33 in vivo, suggesting conserved biological roles of the UL33 gene family.

scholarly journals Poxvirus Complement Control Proteins Are Expressed on the Cell Surface through an Intermolecular Disulfide Bridge with the Viral A56 Protein

2010 ◽  
Vol 84 (21) ◽  
pp. 11245-11254 ◽  
Author(s):  
Brian C. DeHaven ◽  
Natasha M. Girgis ◽  
Yuhong Xiao ◽  
Paul N. Hudson ◽  
Victoria A. Olson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
Surface Expression ◽  
Disulfide Bridge ◽  
Eukaryotic Cell ◽  
Cell Surface Expression ◽  
Complement Control Proteins ◽  
Express Cell ◽  
Infected Cells

ABSTRACT The vaccinia virus (VACV) complement control protein (VCP) is an immunomodulatory protein that is both secreted from and expressed on the surface of infected cells. Surface expression of VCP occurs though an interaction with the viral transmembrane protein A56 and is dependent on a free N-terminal cysteine of VCP. Although A56 and VCP have been shown to interact in infected cells, the mechanism remains unclear. To investigate if A56 is sufficient for surface expression, we transiently expressed VCP and A56 in eukaryotic cell lines and found that they interact on the cell surface in the absence of other viral proteins. Since A56 contains three extracellular cysteines, we hypothesized that one of the cysteines may be unpaired and could therefore form a disulfide bridge with VCP. To test this, we generated a series of A56 mutants in which each cysteine was mutated to a serine, and we found that mutation of cysteine 162 abrogated VCP cell surface expression. We also tested the ability of other poxvirus complement control proteins to bind to VACV A56. While the smallpox homolog of VCP is able to bind VACV A56, the ectromelia virus (ECTV) VCP homolog is only able to bind the ECTV homolog of A56, indicating that these proteins may have coevolved. Surface expression of poxvirus complement control proteins may have important implications in viral pathogenesis, as a virus that does not express cell surface VCP is attenuated in vivo. This suggests that surface expression of VCP may contribute to poxvirus pathogenesis.

Metalloproteinases Are Involved in Lipopolysaccharide– and Tumor Necrosis Factor-–Mediated Regulation of CXCR1 and CXCR2 Chemokine Receptor Expression

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2173-2185 ◽  
Author(s):  
Masud H. Khandaker ◽  
Gordon Mitchell ◽  
Luoling Xu ◽  
Joseph D. Andrews ◽  
Rajkumari Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Tumor Necrosis ◽  
Inflammatory Responses ◽  
Proteinase Inhibitors ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Metalloproteinase Inhibitors ◽  
Necrosis Factor

The neutrophil-specific G-protein–coupled chemokine receptors, CXCR1 and CXCR2, bind with high affinity to the potent chemoattractant interleukin-8 (IL-8). The mechanisms of IL-8 receptor regulation are not well defined, although previous studies have suggested a process of ligand-promoted internalization as a putative regulatory pathway. Herein, we provide evidence for two distinct processes of CXCR1 and CXCR2 regulation. Confocal microscopy data showed a redistribution of CXCR1 expression from the cell surface of neutrophils to internal compartments after stimulation with IL-8, whereas stimulation with bacterial lipopolysaccharide (LPS) or tumor necrosis factor- (TNF-) did not induce CXCR1 internalization but instead mediated a significant loss of membrane-proximal CXCR1 staining intensity. To investigate whether proteolytic cleavage was the mechanism responsible for LPS- and TNF-–induced downmodulation of IL-8 receptors, we tested a panel of proteinase inhibitors. The downmodulation of CXCR1 and CXCR2 by LPS and TNF- was most dramatically inhibited by metalloproteinase inhibitors; 1,10-phenanthroline and EDTA significantly attenuated LPS- and TNF-–induced loss of CXCR1 and CXCR2 cell surface expression. Metalloproteinase inhibitors also blocked the release of CXCR1 cleavage fragments into the cell supernatants of LPS- and TNF-–stimulated neutrophils. In addition, while treatment of neutrophils with LPS and TNF- inhibited IL-8 receptor–mediated calcium mobilization and IL-8–directed neutrophil chemotaxis, both 1,10-phenanthroline and EDTA blocked these inhibitory processes. In contrast, metalloproteinase inhibitors did not affect IL-8–mediated downmodulation of CXCR1 and CXCR2 cell surface expression or receptor signaling. Thus, these findings may provide further insight into the mechanisms of leukocyte regulation during immunologic and inflammatory responses.

The chemokine CCL5 regulates the in vivo cell surface expression of its receptor, CCR5

AIDS ◽  
2008 ◽  
Vol 22 (3) ◽  
pp. 430-432 ◽  
Author(s):  
Yea-Lih Lin ◽  
Clément Mettling ◽  
Pierre Portalès ◽  
Régine Rouzier ◽  
Jacques Clot ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Receptor Ccr5
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