LPS challenge in healthy subjects: an investigation of neutrophil chemotaxis mechanisms involving CXCR1 and CXCR2

International Immunopharmacology
Raminder AulDave Singh

Abstract

LPS inhalation was used to investigate whether sputum supernatant post-LPS challenge increases neutrophil chemotactic activity and to elucidate the role of CXCR1/CXCR2 signalling in this process. 14 healthy non-smoking subjects inhaled 30μg of LPS. Sputum was induced at baseline, 6 and 24h post-LPS challenge. Differential cell counts were determined and supernatants CXCL8, CXCL1, IL-6 and CCL2 levels measured. Peripheral blood neutrophils obtained from healthy volunteers were used for chemotaxis experiments using sputum supernatant. To delineate signalling mechanisms, the effects of a CXCR2/CXCR1 (dual) antagonist (Sch527123) and a CXCR2 specific antagonist (SB656933) were tested. LPS inhalation significantly increased sputum neutrophil counts from 45.3% to 76.7% and 69.3% at 6 and 24h respectively. LPS increased CXCL8, IL-6 and CCL2 levels but not CXCL1. Neutrophil chemotaxis significantly increased (2.7 fold) at 24h compared to baseline. Chemotaxis was inhibited by 79.0% with Sch527123 and 52.0% with SB656933. We conclude that LPS challenge increases sputum supernatant CXCL8 levels, which is associated with increased chemotactic activity which is dependent on both CXCR1 and CXCR2.

References

Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·S A JonesM Baggiolini
Aug 1, 1996·American Journal of Respiratory and Critical Care Medicine·E PizzichiniF E Hargreave
Jan 1, 1997·Annual Review of Immunology·M BaggioliniB Moser
Nov 14, 1997·American Journal of Respiratory and Critical Care Medicine·O MichelR Sergysels
Sep 18, 1999·The European Respiratory Journal·A CapelliC F Donner
Nov 11, 1999·American Journal of Respiratory and Critical Care Medicine·A JatakanonP J Barnes
Jun 13, 2001·American Journal of Respiratory and Critical Care Medicine·N P O'GradyA F Suffredini
Jul 13, 2001·Pulmonary Pharmacology & Therapeutics·C Owen
Jul 5, 2005·American Journal of Respiratory and Critical Care Medicine·Nico A MarisTom van der Poll
Oct 11, 2005·Respiratory Medicine·Suleyman S HacievliyagilIsmail Temel
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
Nov 18, 2006·American Journal of Respiratory and Critical Care Medicine·Takahiro YoshikawaRatko Djukanovic
May 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Waldemar GonsiorekR William Hipkin
Nov 26, 2008·Pharmacology & Therapeutics·R W ChapmanJ S Fine
Nov 29, 2008·The New England Journal of Medicine·Sanjay Sethi, Timothy F Murphy
Jun 6, 2009·European Journal of Immunology·Jörg ReutershanKlaus Ley
Jul 23, 2009·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P MacedoK F Chung
Aug 1, 2009·The European Respiratory Journal·O HolzH Magnussen
May 24, 2011·PloS One·Patrick G ArndtBruce Walcheck

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Citations

Jan 25, 2014·Pulmonary Pharmacology & Therapeutics·Yanira Riffo-VasquezClive P Page
Jan 23, 2016·Science Translational Medicine·Muthulekha SwamydasMichail S Lionakis
Sep 15, 2012·Pulmonary Pharmacology & Therapeutics·Hanna Falk HåkanssonHarbans Lal
Sep 4, 2014·Respiratory Research·Arjun K RaviDave Singh
Feb 22, 2014·Expert Opinion on Therapeutic Patents·Michael P Dwyer, Younong Yu
Feb 20, 2015·American Journal of Respiratory and Critical Care Medicine·Stephen I RennardHeribert Staudinger
Jun 23, 2016·British Journal of Clinical Pharmacology·Virginie DoyenOlivier Michel
Oct 13, 2016·British Journal of Clinical Pharmacology·Anna K StalderJasper Dingemanse
Jun 15, 2017·The Journal of Pharmacology and Experimental Therapeutics·Jakob Busch-PetersenRuth Tal-Singer
Aug 6, 2013·The Journal of Pharmacology and Experimental Therapeutics·Manminder Kaur, Dave Singh
Nov 16, 2013·Current Opinion in Pulmonary Medicine·Zuzana DiamantJuan Gispert
Feb 7, 2015·Expert Review of Clinical Immunology·Stefan ZielenRalf Schubert
Jul 12, 2019·Frontiers in Immunology·Simon SodySven Brandau
Jun 5, 2014·Molecular Pharmaceutics·Helen Ha, Nouri Neamati

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