scholarly journals Role of CXC Chemokine Ligand 13, CC Chemokine Ligand (CCL) 19, and CCL21 in the Organization and Function of Nasal-Associated Lymphoid Tissue

2005 ◽  
Vol 175 (8) ◽  
pp. 4904-4913 ◽  
Author(s):  
Javier Rangel-Moreno ◽  
Juan Moyron-Quiroz ◽  
Kim Kusser ◽  
Louise Hartson ◽  
Hideki Nakano ◽  
...  
2012 ◽  
Vol 442 (2) ◽  
pp. 433-442 ◽  
Author(s):  
Paramita Ray ◽  
Sarah A. Lewin ◽  
Laura Anne Mihalko ◽  
Sasha-Cai Lesher-Perez ◽  
Shuichi Takayama ◽  
...  

Chemokine CXCL12 (CXC chemokine ligand 12) signalling through CXCR (CXC chemokine receptor) 4 and CXCR7 has essential functions in development and underlies diseases including cancer, atherosclerosis and autoimmunity. Chemokines may form homodimers that regulate receptor binding and signalling, but previous studies with synthetic CXCL12 have produced conflicting evidence for homodimerization. We used bioluminescence imaging with GL (Gaussia luciferase) fusions to investigate dimerization of CXCL12 secreted from mammalian cells. Using column chromatography and GL complementation, we established that CXCL12 was secreted from mammalian cells as both monomers and dimers. Secreted CXCL12 also formed homodimers in the extracellular space. Monomeric CXCL12 preferentially activated CXCR4 signalling through Gαi and Akt, whereas dimeric CXCL12 more effectively promoted recruitment of β-arrestin 2 to CXCR4 and chemotaxis of CXCR4-expressing breast cancer cells. We also showed that CXCR7 preferentially sequestered monomeric CXCL12 from the extracellular space and had minimal effects on dimeric CXCL12 in cell-based assays and an orthotopic tumour xenograft model of human breast cancer. These studies establish that CXCL12 secreted from mammalian cells forms homodimers under physiological conditions. Since monomeric and dimeric CXCL12 have distinct effects on cell signalling and function, our results have important implications for ongoing efforts to target CXCL12 pathways for therapy.


2007 ◽  
Vol 104 (25) ◽  
pp. 10577-10582 ◽  
Author(s):  
J. Rangel-Moreno ◽  
J. E. Moyron-Quiroz ◽  
L. Hartson ◽  
K. Kusser ◽  
T. D. Randall

1998 ◽  
Vol 333 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Stephen G. WARD ◽  
John WESTWICK

The chemokines are a complex superfamily of small, secreted proteins that were initially characterized through their chemotactic effects on a variety of leucocytes. The superfamily is divided into families based on structural and genetic considerations and have been termed the CXC, CC, C and CX3C families. Chemokines from these families have a key role in the recruitment and function of T lymphocytes. Moreover, T lymphocytes have also been identified as a source of a number of chemokines. T lymphocytes also express most of the known CXC and CC chemokine receptors to an extent that depends on their state of activation/differentiation and/or the activating stimuli. The expression of two chemokine receptors, namely CXCR4 and CCR5, together with the regulated production of their respective ligands, appears to be extremely important in determining sensitivity of T cells to HIV-1 infection. The intracellular events which mediate the effects of chemokines, particularly those elicited by the CC chemokine RANTES, include activation of both G-protein- and protein tyrosine kinase-coupled signalling pathways. The present review describes our current understanding of the structure and expression of chemokines and their receptors, the effects of chemokines on T-cell function(s), the intracellular signalling pathways activated by chemokines and the role of certain chemokines and chemokine receptors in determining sensitivity to HIV-1 infection.


2005 ◽  
Vol 175 (9) ◽  
pp. 6092-6099 ◽  
Author(s):  
Laurien H. Ulfman ◽  
Jacqueline Alblas ◽  
Corneli W. van Aalst ◽  
Jaap Jan Zwaginga ◽  
Leo Koenderman

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Subramanya N.M. Pandruvada ◽  
Sambandam Yuvaraj ◽  
Xiang Liu ◽  
Kumaran Sundaram ◽  
Srinivasan Shanmugarajan ◽  
...  

2007 ◽  
Vol 179 (3) ◽  
pp. 1740-1750 ◽  
Author(s):  
Jose-Angel Gonzalo ◽  
Yubin Qiu ◽  
Jose M. Lora ◽  
Amal Al-Garawi ◽  
Jean-Luc Villeval ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael Petermann ◽  
Zacharias Orfanos ◽  
Julie Sellau ◽  
Mohammad Gharaibeh ◽  
Hannelore Lotter ◽  
...  

Orientia (O.) tsutsugamushi, the causative agent of scrub typhus, is a neglected, obligate intracellular bacterium that has a prominent tropism for monocytes and macrophages. Complications often involve the lung, where interstitial pneumonia is a typical finding. The severity of scrub typhus in humans has been linked to altered plasma concentrations of chemokines which are known to act as chemoattractants for myeloid cells. The trafficking and function of monocyte responses is critically regulated by interaction of the CC chemokine ligand 2 (CCL2) and its CC chemokine receptor CCR2. In a self-healing mouse model of intradermal infection with the human-pathogenic Karp strain of O. tsutsugamushi, we investigated the role of CCR2 on bacterial dissemination, development of symptoms, lung histology and monocyte subsets in blood and lungs. CCR2-deficient mice showed a delayed onset of disease and resolution of symptoms, higher concentrations and impaired clearance of bacteria in the lung and the liver, accompanied by a slow infiltration of interstitial macrophages into the lungs. In the blood, we found an induction of circulating monocytes that depended on CCR2, while only a small increase in Ly6Chi monocytes was observed in CCR2-/- mice. In the lung, significantly higher numbers of Ly6Chi and Ly6Clo monocytes were found in the C57BL/6 mice compared to CCR2-/- mice. Both wildtype and CCR2-deficient mice developed an inflammatory milieu as shown by cytokine and inos/arg1 mRNA induction in the lung, but with delayed kinetics in CCR2-deficient mice. Histopathology revealed that infiltration of macrophages to the parenchyma, but not into the peribronchial tissue, depended on CCR2. In sum, our data suggest that in Orientia infection, CCR2 drives blood monocytosis and the influx and activation of Ly6Chi and Ly6Clo monocytes into the lung, thereby accelerating bacterial replication and development of interstitial pulmonary inflammation.


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