Neuropeptide substance P upregulates chemokine and chemokine receptor expression in primary mouse neutrophils

2007 ◽  
Vol 293 (2) ◽  
pp. C696-C704 ◽  
Author(s):  
Jia Sun ◽  
Raina Devi Ramnath ◽  
Madhav Bhatia
Keyword(s):  
Substance P ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Activity ◽  
Receptor Expression ◽  
Chemokine Production ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Primary Mouse ◽  
Cxc Chemokine

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.

scholarly journals Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes.

1996 ◽  
Vol 184 (2) ◽  
pp. 569-577 ◽  
Author(s):  
P Loetscher ◽  
M Seitz ◽  
M Baggiolini ◽  
B Moser
Keyword(s):  
T Lymphocytes ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Activated T Cells ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Cc Chemokines

Several studies have shown that CC chemokines attract T lymphocytes, and that CD45RO+, memory phenotype cells are considered to be the main responders. The results, however, have often been contradictory and the role of lymphocyte activation and proliferation has remained unclear. Using CD45RO+ blood lymphocytes cultured under different stimulatory conditions, we have now studied chemotaxis as well as chemokine receptor expression. Expression of the RANTES/MIP-1 alpha receptor (CC-CKR1) and the MCP-1 receptor (CC-CKR2) was highly correlated with migration toward RANTES, MCP-1, and other CC chemokines, and was strictly dependent on the presence of IL-2 in the culture medium. Migration and receptor expression were rapidly downregulated when IL-2 was withdrawn, but were fully restored when IL-2 was added again. The effect of IL-2 could be partially mimicked by IL-4, IL-10, or IL-12, but not by IL-13, IFN gamma, IL-1 beta, TNF-alpha, or by exposure to anti-CD3, anti-CD28 or phytohemagglutinin. Activation of fully responsive lymphocytes through the TCR/CD3 complex and CD28 antigen actually had the opposite effect. It rapidly downregulated receptor expression and consequent migration even in the presence of IL-2. In contrast to the effects on CC chemokine receptors, stimulation of CD45RO+ T lymphocytes with IL-2 neither induced the expression of the CXC chemokine receptors, IL8-R1 and IL8-R2, nor chemotaxis to IL-8. The prominent role of IL-2 in CC chemokine responsiveness of lymphocytes suggests that IL-2-mediated expansion is a prerequisite for the recruitment of antigen-activated T cells into sites of immune and inflammatory reactions.

scholarly journals Identification of a novel mechanism for endotoxin-mediated down-modulation of CC chemokine receptor expression

2000 ◽  
Vol 30 (1) ◽  
pp. 227-235 ◽  
Author(s):  
Luoling Xu ◽  
Masud H. Khandaker ◽  
Jana Barlic ◽  
Longsi Ran ◽  
Miren L. Borja ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine

scholarly journals Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

2001 ◽  
Vol 85 (6) ◽  
pp. 891-897 ◽  
Author(s):  
C Scotton ◽  
D Milliken ◽  
J Wilson ◽  
S Raju ◽  
F Balkwill
Keyword(s):  
Chemokine Receptor ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Ovarian Tumours

Coreceptor/Chemokine Receptor Expression on Human Hematopoietic Cells: Biological Implications for Human Immunodeficiency Virus–Type 1 Infection

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1145-1156 ◽  
Author(s):  
Benhur Lee ◽  
Janina Ratajczak ◽  
Robert W. Doms ◽  
Alan M. Gewirtz ◽  
Mariusz Z. Ratajczak
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Hematopoietic Cells ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
Γ Interferon ◽  
Hiv 1

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.

CC chemokine receptor expression in childhood asthma is influenced by natural allergen exposure

2006 ◽  
Vol 17 (7) ◽  
pp. 495-500 ◽  
Author(s):  
Peroni G. Diego ◽  
Panina Bordignon Paola ◽  
Piacentini L. Giorgio ◽  
Bodini Alessandro ◽  
Ress Michela ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Childhood Asthma ◽  
Allergen Exposure ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine
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