Desensitization of Chemokine Receptor CCR5 in Dendritic Cells at the Early Stage of Differentiation by Activation of Formyl Peptide Receptors

2001 ◽  
Vol 99 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Yingying Le ◽  
Michele A. Wetzel ◽  
Weiping Shen ◽  
Wanghua Gong ◽  
Thomas J. Rogers ◽  
...  
Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2887-2894 ◽  
Author(s):  
Weiping Shen ◽  
Baoqun Li ◽  
Michele A. Wetzel ◽  
Thomas J. Rogers ◽  
Earl E. Henderson ◽  
...  

Abstract Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C–mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein–mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1982-1982 ◽  
Author(s):  
Kifah Shahin ◽  
Mary M Sartor ◽  
Derek NJ Hart ◽  
Kenneth F Bradstock

Abstract Abstract 1982 Introduction: Dendritic cells (DC) are centrally involved in the development of acute graft-versus-host disease (GvHD) following allogeneic hemopoietic cell transplantation (alloHCT). We previously showed that the activation status, as assessed by CMRF-44 antigen expression, of CD11c+ myeloid blood DC is highly associated with the onset and severity of acute GvHD (Transplantation. 2007;83:839–846). We also reported a positive correlation between acute GvHD and the expression of the chemokine receptor CCR5 on CD11c+ myeloid DC (Blood. 2009;114 Suppl.:2251). Given the phenotypic and functional heterogeneity of the CD11c+ DC population, we investigated CCR5 expression on the CD11c+ DC subsets and then monitored the informative CD11c+ CD16+ DC subset expression of CCR5 in the peripheral blood of 42 patients post alloHCT, and correlated the findings with GvHD. Methods: Peripheral blood was collected twice weekly up to Day 100 post transplant from 42 alloHCT patients. The expression of CCR5 receptor on CD11c+ and CD11c- DC subsets was evaluated using multiparameter flow cytometry. Results: Only the CD11c+ CD16+ DC subset lacked CCR5 and induced it upon alloactivation. Seventeen of 42 patients developed acute GvHD (5 grade I, 12 grades II-IV). The percentage of CD11c+ CD16+ DC expressing CCR5 correlated with the development of acute GvHD grades II-IV. The maximum CCR5 expression detected on CD11c+ CD16+ DC in patients prior to developing grades II-IV GvHD (mean 22.7 ± 4.3%, n=12) was higher than in those with grades 0-I GvHD (11.4 ± 1.7%, n=30) (p=0.0285). CCR5 levels >20% on CD16+ myeloid DC predicted grades II-IV GvHD with a sensitivity of 66.7% and specificity of 86.7%. Levels of expression of CCR5 on the CD11c+ CD16- DC and CD123+ plasmacytoid DC were not predictive of GvHD. Conclusion: Expression of CCR5 on circulating CD11c+ CD16+ myeloid DC post alloHCT correlated with the development of moderate to severe GvHD. This observation may reflect DC activation or altered DC homing during the alloimmune response. Detection of increased CCR5+ CD11c+ CD16+ DC may allow pre-emptive therapeutic intervention prior to the clinical diagnosis of GvHD. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
A. P. Freitas ◽  
B. C. Favoretto ◽  
P. B. Clissa ◽  
S. C. Sampaio ◽  
E. L. Faquim-Mauro

TheCrotalus durissus terrificusrattlesnake venom, its main toxin, crotoxin (CTX), and its crotapotin (CA) and phospholipase A2(CB) subunits modulate the immune system. Formyl peptide receptors (FPRs) and lipoxin A4(LXA4) are involved in CTX’s effect on macrophages and neutrophils. Dendritic cells (DCs) are plasticity cells involved in the induction of adaptive immunity and tolerance maintenance. Therefore, we evaluated the effect of CTX, CA or CB on the maturation of DCs derived from murine bone marrow (BM). According to data, CTX and CB—but not CA—induced an increase of MHC-II, but not costimulatory molecules on DCs. Furthermore, CTX and CB inhibited the expression of costimulatory and MHC-II molecules, secretion of proinflammatory cytokines and NF-κBp65 and p38/ERK1/2-MAPK signaling pathways by LPS-incubated DCs. Differently, CTX and CB induced IL-10, PGE2and LXA4secretion in LPS-incubated DCs. Lower proliferation and IL-2 secretion were verified in coculture of CD3+cells and DCs incubated with LPS plus CTX or CB compared with LPS-incubated DCs. The effect of CTX and CB on DCs was abolished in cultures incubated with a FPRs antagonist. Hence, CTX and CB exert a modulation on functional activity of DCs; we also checked the involvement the FPR family on cell activities.


Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2887-2894
Author(s):  
Weiping Shen ◽  
Baoqun Li ◽  
Michele A. Wetzel ◽  
Thomas J. Rogers ◽  
Earl E. Henderson ◽  
...  

Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C–mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein–mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents.


2003 ◽  
Vol 2 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Yingying Le ◽  
Ronghua Sun ◽  
Guoguang Ying ◽  
Pablo Iribarren ◽  
Ji Wang

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