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

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• 作者：Raminder Aul^a ; ¹ ; ^{Raul@meu.org.uk} ; Sheena Patel^b ; ¹ ; ^{Sheena.Patel@pfizer.com} ; Susan Summerhill^b ; ^{Susan.Summerhill@pfizer.com} ; Iain Kilty^b ; ^{Iain.Kilty@pfizer.com} ; Jonathan Plumb^a ; ^{jonathan.plumb@manchester.ac.uk} ; Dave Singh^a ; ^{Dsingh@meu.org.uk}
• 关键词：COPD ; Chemotaxis ; Neutrophils ; CXCR1 ; CXCR2 ; Lipopolysaccharide
• 刊名：International Immunopharmacology
• 出版年：2012
• 期刊代码：123_15675769
• 类别：med
• 出版时间：July, 2012
• 卷：13
• 期：3
• 页码：225-231
• 文件大小：635 K

摘要

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 30 渭g of LPS. Sputum was induced at baseline, 6 and 24 h 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 24 h respectively. LPS increased CXCL8, IL-6 and CCL2 levels but not CXCL1. Neutrophil chemotaxis significantly increased (2.7 fold) at 24 h 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.