Channelpedia

PubMed 18208820


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1 , Slo1



Title: Abnormal in vitro CXCR2 modulation and defective cationic ion transporter expression on polymorphonuclear neutrophils responsible for hyporesponsiveness to IL-8 stimulation in patients with active systemic lupus erythematosus.

Authors: S-C Hsieh, T-H Wu, C-Y Tsai, K-J Li, M-C Lu, C-H Wu, C-L Yu

Journal, date & volume: Rheumatology (Oxford), 2008 Feb , 47, 150-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18208820


Abstract
To elucidate the molecular basis of hyporesponsiveness of polymorphonuclear neutrophils (PMN) to interleukin-8 (IL-8) stimulation in patients with active SLE.PMN obtained from active SLE and well-matched healthy individuals were studied. The expression of two IL-8 receptors, CXCR1 and CXCR2, in PMN were detected by flow cytometry and reverse transcriptase-polymerase chain reaction. The binding affinity of PMN with IL-8 was calculated by Scatchard plotting. Soluble CXCR2 level in IL-8-stimulated PMN culture supernatant was measured by sandwich enzyme-linked immunosorbent assay. The resting and IL-8-stimulated membrane potential (MP) changes, and membrane expression of cationic ion transporters including Na+-K+-ATPase, renal epithelial Na+ channel (ENaC) and renal outer medullary epithelial K+ channel 1 (ROMK1) on PMN were detected by flow cytometry.Compared with normal PMN, decreased CXCR2 gene expression, but normal IL-8-binding affinity of SLE-PMN, was found. For exploring the molecular basis of the defect, the modulation of CXCR2 in SLE-PMN was intensively investigated. We found that increased cytosolic CXCR2 expression in SLE-PMN was due to defective surface translocation, increased spontaneous internalization and/or increased spontaneous synthesis. The IL-8-induced CXCR2 down-regulation in SLE-PMN was also impaired due to decreased proteolytic cleavage of IL-8-IL-8 receptor complexes from the cell surface whereas IL-8-induced internalization of the complexes was normal. In addition, we originally found that increased resting but decreased IL-8-stimulated MP in SLE-PMN was relevant to defective expression of Na+-K+-ATPase, ENaC and ROMK1 on the cell surface.The abnormal CXCR2 modulation and impaired cationic ion transporter expression cause SLE-PMN hyporesponsiveness to IL-8 stimulation in vitro.