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Int Immunopharmacol. 2012 Jul;13(3):225-31. doi: 10.1016/j.intimp.2012.04.008. Epub 2012 May 2.

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

Author information

1
University of Manchester, Medicines Evaluation Unit, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, Manchester, UK. Raul@meu.org.uk

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.

PMID:
22561413
DOI:
10.1016/j.intimp.2012.04.008
[Indexed for MEDLINE]

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