The atypical chemokine receptor ACKR2 is protective against sepsis

Castanheira, F. V. E. S. et al. (2018) The atypical chemokine receptor ACKR2 is protective against sepsis. Shock, 49(6), pp. 682-689. (doi: 10.1097/SHK.0000000000000969) (PMID:29589840)

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Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ACKR2 is an atypical chemokine receptor, which can remove and degrade inflammatory CC chemokines. The role of ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we demonstrate here that ACKR2 deficient (−/−) mice exhibited a significant reduction in the survival rate compared to similarly treated wild type (WT) mice. However, neutrophil migration to the peritoneal cavity and bacterial load were similar between WT and ACKR2−/− mice during CLP. In contrast, ACKR2−/− mice showed increased neutrophil infiltration and elevated CC chemokine levels in the lung, kidney and heart compared to the WT mice. In addition, ACKR2−/− mice also showed more severe lesions in the lung and kidney than those in the WT mice. Consistent with these results, WT mice under non-severe sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2+ cells compared to those of non-septic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration and damage to vital organs.

Item Type:Articles
Additional Information:This work was supported by grants from the São Paulo Research Foundation (FAPESP) 2011/19670-0 (Thematic project), 2013/08216-2 (Center for Research in Inflammatory Disease, CRID), CAPES, CNPq and from the European Union Seventh Framework Program [FP7-2007- 2013, HEALTH-F4-2011-281608 (TIMER)] and from the University of São Paulo NAP-DIN (11.1.21625.01.0).
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Graham, Professor Gerard
Authors: Castanheira, F. V. E. S., Borges, V., Sônego, F., Kanashiro, A., Donate, P. B., Melo, P. H., Pallas, K., Russo, R. C., Amaral, F. A., Teixeira, M. M., Ramalho, F. S., Cunha, T. M., Liew, F. Y., Alves-Filho, J. C., Graham, G. J., and Cunha, F. Q.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Shock
Publisher:Lippincott, Williams & Wilkins
ISSN (Online):1540-0514
Published Online:24 August 2017
Copyright Holders:Copyright © 2017 The Shock Society
First Published:First published in Shock 49(6): 682-689
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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