scholarly journals Leishmania major Modulates Chemokine and Chemokine Receptor Expression by Dendritic Cells and Affects Their Migratory Capacity

2005 ◽  
Vol 73 (4) ◽  
pp. 2564-2567 ◽  
Author(s):  
Mario Steigerwald ◽  
Heidrun Moll

ABSTRACT Dendritic cells (DC) both produce and respond to chemokines. We examined the profiles of chemokines and chemokine receptors expressed by DC and their chemotactic response after interaction with Leishmania major. Expression of the chemokine receptors CCR2 and CCR5 by DC and their responsiveness to the respective ligands, CCL2 and CCL3, were downregulated, while the level of CCR7 and the DC response to its ligand CCL21 were enhanced. These parasite-induced alterations were observed with DC from L. major-resistant and -susceptible mice. In contrast, expression of the chemokine CXCL10 was elicited only in DC from L. major-resistant mice.

2008 ◽  
Vol 6 (2) ◽  
pp. 175-185 ◽  
Author(s):  
Annamaria Ricciardi ◽  
Angela Rita Elia ◽  
Paola Cappello ◽  
Maura Puppo ◽  
Cristina Vanni ◽  
...  

2007 ◽  
Vol 293 (2) ◽  
pp. C696-C704 ◽  
Author(s):  
Jia Sun ◽  
Raina Devi Ramnath ◽  
Madhav Bhatia

Neuropeptides play an important role in the active communication between the nervous and immune systems. Substance P (SP) is a prominent neuropeptide involved in neurogenic inflammation and has been reported to exert various proinflammatory actions on inflammatory leukocytes including neutrophils. The present study further investigated the modulatory effect of SP (1 μM) on chemokine production and chemokine receptor expression in primary mouse neutrophils. Our results showed that SP primed neutrophils for chemotactic responses not only to the CXC chemokine macrophage inflammatory protein (MIP)-2/CXCL2 but also to the CC chemokine MIP-1α/CCL3. The activating effect of SP on neutrophils was further evidenced by upregulation of the CD11b integrin, the activation marker of neutrophils. SP induced both the mRNA and protein expression of the chemokines MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils and upregulated the chemokine receptors CC chemokine receptor (CCR)-1 and CXC chemokine receptor (CXCR)-2. This stimulatory effect on chemokine and chemokine receptor expression in neutrophils was further found to be neurokinin-1 receptor (NK-1R) specific. Pretreatment with selective NK-1R antagonists inhibited SP-triggered activation of neutrophils and chemokine and chemokine receptor upregulation. Moreover, SP-induced chemokine upregulation was NF-κB dependent. SP time dependently induced NF-κB p65 binding activity, IκBα degradation, and NF-κB p65 nuclear translocation in neutrophils. Inhibition of NF-κB activation with its inhibitor Bay11-7082 (10 μM) abolished SP-induced NF-κB binding activity and upregulation of MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils. Together, these results suggest that SP exerts a direct stimulatory effect on the expression of chemokines and chemokine receptors in mouse neutrophils. The effect is NK-1R mediated, involving NF-κB activation.


Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1145-1156 ◽  
Author(s):  
Benhur Lee ◽  
Janina Ratajczak ◽  
Robert W. Doms ◽  
Alan M. Gewirtz ◽  
Mariusz Z. Ratajczak

Abstract The recent discovery of chemokine receptors as coreceptors for human immunodeficiency virus–type 1 (HIV-1) entry offers new avenues for investigating the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related cytopenias. To this end, we sought to (1) phenotype human hematopoietic cells for CD4 and the HIV-1 coreceptors CXCR4, CCR5, CCR3, and CCR2b; (2) correlate CD4 and chemokine receptor expression with their susceptibility to HIV-1 infection; and (3) examine any potential interplay between inflammatory cytokines released during HIV-1 infection and regulation of chemokine receptor expression. Fluorescence-activated cell sorting (FACS) analysis of bone marrow mononuclear cells (BMMNC), cells derived from serum-free expanded hematopoietic lineages (colony-forming unit–granulocyte-macrophage [CFU-GM], colony-forming unit-megakaryocyte [CFU-Meg], and burst-forming unit-erythroid [BFU-E]), and CD34+ cells showed differential expression of chemokine receptors and CD4 with some lineage specificity. Significantly, FACS-sorted CXCR4+/CD34+ cells had the same clonogeneic potential as CXCR4−/CD34+ cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of FACS-sorted human candidate stem cells (HSC; CD34+, c-kit+, Rho123low) showed the presence of CXCR4 mRNA but not CD4 mRNA. Infection studies with HIV-1 Env-pseudotyped luciferase reporter viruses indicated that X4 Env (CXCR4-using) pseudotypes infected megakaryocytic cells, whereas R5 Env (CCR5-using) pseudotypes did not. Similarly, R5 but not X4 Env-pseudotyped viruses infected granulocyte-macrophage cells in a CD4/CCR5-dependent manner. Erythroid cells were resistant to R5 or X4 viral infection. Finally, we found that γ-interferon treatment upregulated CXCR4 expression on primary hematopoietic cells. In summary, the delineation of chemokine receptor expression on primary hematopoietic cells is a first step towards dissecting the chemokine-chemokine receptor axes that may play a role in hematopoietic cell proliferation and homing. Furthermore, susceptibility of hematopoietic cells to HIV-1 infection is likely to be more complicated than the mere physical presence of CD4 and the cognate chemokine receptor. Lastly, our results suggest a potential interplay between γ-interferon secretion and CXCR4 expression.


Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1145-1156 ◽  
Author(s):  
Benhur Lee ◽  
Janina Ratajczak ◽  
Robert W. Doms ◽  
Alan M. Gewirtz ◽  
Mariusz Z. Ratajczak

The recent discovery of chemokine receptors as coreceptors for human immunodeficiency virus–type 1 (HIV-1) entry offers new avenues for investigating the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related cytopenias. To this end, we sought to (1) phenotype human hematopoietic cells for CD4 and the HIV-1 coreceptors CXCR4, CCR5, CCR3, and CCR2b; (2) correlate CD4 and chemokine receptor expression with their susceptibility to HIV-1 infection; and (3) examine any potential interplay between inflammatory cytokines released during HIV-1 infection and regulation of chemokine receptor expression. Fluorescence-activated cell sorting (FACS) analysis of bone marrow mononuclear cells (BMMNC), cells derived from serum-free expanded hematopoietic lineages (colony-forming unit–granulocyte-macrophage [CFU-GM], colony-forming unit-megakaryocyte [CFU-Meg], and burst-forming unit-erythroid [BFU-E]), and CD34+ cells showed differential expression of chemokine receptors and CD4 with some lineage specificity. Significantly, FACS-sorted CXCR4+/CD34+ cells had the same clonogeneic potential as CXCR4−/CD34+ cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of FACS-sorted human candidate stem cells (HSC; CD34+, c-kit+, Rho123low) showed the presence of CXCR4 mRNA but not CD4 mRNA. Infection studies with HIV-1 Env-pseudotyped luciferase reporter viruses indicated that X4 Env (CXCR4-using) pseudotypes infected megakaryocytic cells, whereas R5 Env (CCR5-using) pseudotypes did not. Similarly, R5 but not X4 Env-pseudotyped viruses infected granulocyte-macrophage cells in a CD4/CCR5-dependent manner. Erythroid cells were resistant to R5 or X4 viral infection. Finally, we found that γ-interferon treatment upregulated CXCR4 expression on primary hematopoietic cells. In summary, the delineation of chemokine receptor expression on primary hematopoietic cells is a first step towards dissecting the chemokine-chemokine receptor axes that may play a role in hematopoietic cell proliferation and homing. Furthermore, susceptibility of hematopoietic cells to HIV-1 infection is likely to be more complicated than the mere physical presence of CD4 and the cognate chemokine receptor. Lastly, our results suggest a potential interplay between γ-interferon secretion and CXCR4 expression.


Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3032-3043 ◽  
Author(s):  
Craig Murdoch ◽  
Adam Finn

Chemokines are small peptides that are potent activators and chemoattractants for leukocyte subpopulations and some nonhemopoietic cells. Their actions are mediated by a family of 7-transmembrane G-protein–coupled receptors, the size of which has grown considerably in recent years and now includes 18 members. Chemokine receptor expression on different cell types and their binding and response to specific chemokines are highly variable. Significant advances have been made in understanding the regulation of chemokine receptor expression and the intracellular signaling mechanisms used in bringing about cell activation. Chemokine receptors have also recently been implicated in several disease states including allergy, psoriasis, atherosclerosis, and malaria. However, most fascinating has been the observation that some of these receptors are used by human immunodeficiency virus type 1 in gaining entry into permissive cells. This review will discuss structural and functional aspects of chemokine receptor biology and will consider the roles these receptors play in inflammation and in infectious diseases.


Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1109-1116 ◽  
Author(s):  
Uta E. Höpken ◽  
Hans-Dieter Foss ◽  
Dagmar Meyer ◽  
Michael Hinz ◽  
Korinna Leder ◽  
...  

Chemokines and chemokine receptors are key mediators for regulating cell traffic and positioning in both homeostatic and inflammatory conditions. It is also presumed that chemokines and their receptors are likely to play a critical role in the localization of malignant hematopoietic cells in their target organs. This study analyzed chemokine and chemokine receptor expression in several Hodgkin disease (HD)–derived cell lines and in HD tumors. All HD-derived cell lines expressed functional CCR7 and CXCR4 receptors. CCR7 up-regulation was mediated by constitutive NF-κB activity. Lymphoid tissues in HD revealed differential expression levels of CCR7, CXCR4, and CXCR5, depending on the distinct subtypes of HD. HD of the classical subtypes, predominantly located in the interfollicular zone, showed strong CCR7 and CXCR4 expression and moderate CXCR5 expression. In contrast, the nodular lymphocyte-predominant HD (NLP) subtype, regularly associated with follicular structures, exhibited no CCR7 reactivity but abundant CXCR4 staining. Their respective chemokine ligands showed marked expression by reactive cells within the tumors of classical HD and outside of the tumor nodules in NLPHD. Functionally, such differential chemokine receptor expression might contribute to specific localization and confinement of neoplastic cells within the target organs in the distinct HD entities.


1998 ◽  
Vol 149 (7-8) ◽  
pp. 639-641 ◽  
Author(s):  
A. Mantovani ◽  
P. Allavena ◽  
A. Vecchi ◽  
S. Sozzani

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