Role of Transient Receptor Potential Vanilloid 4 for the Development of Acute Lung Injury in Pneumococcal Pneumonia

B Schneider; B Gutbier; K Reppe; J Lienau; L Michalik; L Erfinanda; A Lask; N Suttorp; WM Kübler; M Witzenrath

doi:10.1055/s-0037-1619300

Pneumologie, Table of Contents

Pneumologie 2018; 72(S 01): S69
DOI: 10.1055/s-0037-1619300

Sektion 14 – Zellbiologie

Freie Vorträge – Titel: Freie Vorträge der Sektion Zellbiologie

Georg Thieme Verlag KG Stuttgart · New York

Role of Transient Receptor Potential Vanilloid 4 for the Development of Acute Lung Injury in Pneumococcal Pneumonia

B Schneider

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

B Gutbier

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

K Reppe

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

J Lienau

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

L Michalik

²Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Physiology and Center for Cardiovascular Research

,

L Erfinanda

²Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Physiology and Center for Cardiovascular Research

,

A Lask

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

N Suttorp

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

,

WM Kübler

²Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Physiology and Center for Cardiovascular Research

,

M Witzenrath

¹Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Infectious Diseases and Pulmonary Medicine

› Author Affiliations

Abstract

Full Text

Introduction:

In severe pneumonia, pathogen-host interaction evokes inflammation and pulmonary endothelial barrier disruption resulting in acute lung injury (ALI) despite antibiotic therapy. Preventive strategies for pneumonia patients with a high risk to develop acute lung injury are missing. The cation channel transient receptor potential vanilloid 4 (TRPV4) regulates cellular Ca2+ influx and is involved in inflammatory responses of endothelial cells and leukocytes. However, the role of the TRPV4 channel in severe pneumonia has not been examined.

Methods:

Female TRPV4 knockout (TRPV4-KO) and wildtype (WT) C57Bl/6J mice were infected with Streptococcus pneumoniae. To quantify lung permeability, human serum albumin (HSA) was intravenously injected 47h after infection and 1h thereafter mice were exsanguinated, bronchoalveolar lavage (BAL) performed and HSA- BAL/plasma ratio calculated. Leukocytes from blood and BAL were analyzed by hemocytometer and FACS, and bacterial colony forming units (CFUs) quantified.

Results:

Pulmonary recruitment of leukocytes, bacterial load in BALF and lung hyperpermeability were significantly reduced in TRPV4-KO mice in comparison to WT animals. In blood, leukocyte counts and CFUs were not different between TRPV4-KO and WT-mice.

Conclusion:

The current data suggest that targeting the TRPV4 channel may provide a therapeutic perspective in severe pneumococcal pneumonia. Further investigations are warranted to gain mechanistic insights.