Pneumologie 2018; 72(03): 227
DOI: 10.1055/s-0037-1615316
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Georg Thieme Verlag KG Stuttgart · New York

Role of neutrophil-attractant CXCL5/LIX in barrier damage in ventilator-induced lung injury and pneumococcal pneumonia

S Berger
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
SM Wienhold
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
C Gökeri
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
U Behrendt
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
H Müller-Redetzky
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
K Dietert
2   Freie Universität Berlin, Institute of Veterinary Pathology, Berlin, Germany
,
AD Gruber
2   Freie Universität Berlin, Institute of Veterinary Pathology, Berlin, Germany
,
M Witzenrath
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
,
G Nouailles
1   Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
07 March 2018 (online)

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Neutrophil recruitment to the site of inflammation is a crucial step in the defense against numerous bacterial infections and is partly driven by the chemokine receptor CXCR2 and its pneumocyte-derived ligand CXCL5/LIX. However, excessive accumulation of polymorphonuclear leukocytes (PMNs) can result in life-threatening host tissue injury. Using murine models of ventilator-induced lung injury (VILI) and pneumococcal pneumonia in CXCL5-deficient (CXCL5-/-) and wild-type (WT) mice, we studied the role of CXCL5 and neutrophils in acute lung injury (ALI).

Following high tidal volume mechanical ventilation, we observed a significant reduction in alveolar PMN recruitment, accompanied by reduced vascular leakage in CXCL5-/- mice compared to WT mice. Accordingly, in response to intranasal Streptococcus pneumonia (S. pn.) infection, PMN recruitment into alveolar spaces was dependent on CXCL5 signaling. Hence, reduced PMN numbers resulted in increased bacterial burden in CXCL5-/- compared to WT mice. However, survival rates remained unaffected. Notably, despite elevated bacterial burden in pneumococcal pneumonia, the absence of CXCL5 resulted in reduced vascular leakage in both models, VILI and bacteria-induced lung injury.

Our results highlighted the interplay of CXCL5 and neutrophils and their impact on the alveolar-capillary barrier in development of ALI. Future studies aim at understanding the underlying mechanisms of barrier disruption as prerequisite for the improvement of novel lung-protective ventilation strategies and antimicrobial therapies.