title: Regulation of human neutrophil chemokine receptor expression and function by activation of Toll-like receptors 2 and 4.
abstract: Neutrophil chemokine receptor expression can be altered by exposure to Toll-like receptor (TLR) agonists, a process that is thought to have the potential to localize neutrophils to sites of infection. In order to investigate this process in more detail, we examined the regulation of highly pure neutrophil CXCR1 and CXCR2 expression and function by selective agonists of TLR2 (Pam(3)CSK(4)) and TLR4 (lipopolysaccharide, LPS). CXCR1 and CXCR2 were down-regulated by TLR engagement. CXCR2 loss was more rapid and showed a dependence upon soluble helper molecules (LPS binding protein and CD14) that was not evident for CXCR1, suggesting differential coupling of LPS signalling to CXCR1 and CXCR2 loss. However, TLR engagement in highly pure neutrophils did not result in complete loss of chemokine receptors, and LPS-treated neutrophils remained able to mount a respiratory burst to CXCL8 and CXCL1, and were able to migrate towards CXCL8 in assays of under-agarose chemotaxis. Thus, although treatment of purified human neutrophils with TLR2 and TLR4 agonists modifies chemokine receptor expression, remaining receptors remain functionally competent.
authors.affiliation: Academic Units of Respiratory Medicine, Section of Functional Genomics, Division of Genomic Medicine, University of Sheffield, Sheffield, UK. i.sabroe@sheffield.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jones
authors.forename: Moira K B
authors.initials: MK
authors.lastname: Whyte
authors.forename: Steven K
authors.initials: SK
authors.lastname: Dower
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000819:agonists / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018836:Inflammation Mediators; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099231:Lipopolysaccharide-Binding Protein; C495342:TLR2 protein, human; C495345:TLR4 protein, human