A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.

Autor:	Toya S; Dompé Farmaceutici S.p.A, Milan, Italy sophie.toya@dompe.com., Struyf S; KU Leuven, Department of Microbiology, Immunology and Transplantation, Leuven, Belgium., Huerta L; Keck School of Medicine of USC, Department of Medicine, Pulmonary and Critical Care Medicine, Los Angeles, CA, USA., Morris P; The University of Alabama at Birmingham, Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine, Birmingham, AL, USA., Gavioli E; Dompé Farmaceutici S.p.A, Milan, Italy., Minnella EM; Dompé Farmaceutici S.p.A, Milan, Italy., Cesta MC; Dompé Farmaceutici S.p.A, Milan, Italy., Allegretti M; Dompé Farmaceutici S.p.A, Milan, Italy., Proost P; KU Leuven, Department of Microbiology, Immunology and Transplantation, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2024 Jul 24; Vol. 33 (173). Date of Electronic Publication: 2024 Jul 24 (Print Publication: 2024).
DOI:	10.1183/16000617.0172-2023
Abstrakt:	Acute respiratory distress syndrome (ARDS) is a severe form of acute respiratory failure characterised by extensive inflammatory injury to the alveolocapillary barrier leading to alveolar oedema, impaired gas exchange and, ultimately, hypoxaemia necessitating the use of supplemental oxygen combined with some degree of positive airway pressure. Although much heterogeneity exists regarding the aetiology, localisation and endotypic characterisation of ARDS, what remains largely undisputed is the role of the innate immune system, and in particular of neutrophils, in precipitating and propagating lung injury. Activated neutrophils, recruited to the lung through chemokine gradients, promote injury by releasing oxidants, proteases and neutrophil extracellular traps, which ultimately cause platelet aggregation, microvascular thrombosis and cellular death. Among various neutrophilic chemoattractants, interleukin-8/C-X-C motif ligand 8 and related chemokines, collectively called ELR+ chemokines, acting on neutrophils through the G protein-coupled receptors CXCR1 and CXCR2, are pivotal in orchestrating the neutrophil activation status and chemotaxis in the inflamed lung. This allows efficient elimination of infectious agents while at the same time minimising collateral damage to host tissue. Therefore, understanding how CXCR1 and CXCR2 receptors are regulated is important if we hope to effectively target them for therapeutic use in ARDS. In the following narrative review, we provide an overview of the role of ELR+ chemokines in acute lung injury (ALI) and ARDS, we summarise the relevant regulatory pathways of their cognisant receptors CXCR1/2 and highlight current preclinical and clinical evidence on the therapeutic role of CXCR1 and CXCR2 inhibition in animal models of ALI, as well as in ARDS patients. Competing Interests: Conflict of interest: S. Toya, E. Gavioli, E.M. Minnella, M.C. Cesta and M. Allegretti are Dompé employees. P. Morris and L. Huerta act as Principal Investigators in studies currently conducted by Dompé and have received consulting fees for expertise in critical care clinical trials (P. Morris) as well as travel reimbursements for participating in study start-up investigators meetings (P. Morris and L. Huerta). P. Proost and S. Struyf declare no conflict of interest. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
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