title: Airway smooth muscle chemokine receptor expression and function in asthma.
abstract: BACKGROUND
  Chemokine receptors play an important role in cell migration and wound repair. In asthma, CCR3 and 7 are expressed by airway smooth muscle (ASM) and CCR7 has been implicated in the development of ASM hyperplasia. The expression profile of other chemokine receptors by ASM and their function needs to be further explored.
  
  
  OBJECTIVE
  We sought to investigate ASM chemokine receptor expression and function in asthma.
  
  
  METHODS
  ASM cells were derived from 17 subjects with asthma and 36 non-asthmatic controls. ASM chemokine receptor expression was assessed by flow cytometry and immunofluorescence. The function of chemokine receptors expressed by more than 10% of ASM cells was investigated by intracellular calcium measurements, chemotaxis, wound healing, proliferation and survival assays.
  
  
  RESULTS
  In addition to CCR3 and 7, CXCR1, 3 and 4 were highly expressed by ASM. These CXC chemokine receptors were functional with an increase in intracellular calcium following ligand activation and promotion of wound healing [CXCL10 (100 ng/mL) 34 +/- 2 cells/high-powered field (hpf) vs. control 29 +/- 1; P=0.03; n=8]. Spontaneous wound healing was inhibited by CXCR3 neutralizing antibody (mean difference 7 +/- 3 cells/hpf; P=0.03; n=3). CXC chemokine receptor activation did not modulate ASM chemotaxis, proliferation or survival. No differences in chemokine receptor expression or function were observed between ASM cells derived from asthmatic or non-asthmatic donors.
  
  
  CONCLUSIONS
  Our findings suggest that the chemokine receptors CXCR1, 3 and 4 modulate some aspects of ASM function but their importance in asthma is uncertain.
authors.affiliation: Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Saunders
authors.forename: A
authors.initials: A
authors.lastname: Sutcliffe
authors.forename: D
authors.initials: D
authors.lastname: Kaur
authors.forename: S
authors.initials: S
authors.lastname: Siddiqui
authors.forename: F
authors.initials: F
authors.lastname: Hollins
authors.forename: A
authors.initials: A
authors.lastname: Wardlaw
authors.forename: P
authors.initials: P
authors.lastname: Bradding
authors.forename: C
authors.initials: C
authors.lastname: Brightling
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000096:biosynthesis*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019707:Receptors, Chemokine; D002118:Calcium