title: CCR3 expression and function in asthmatic airway smooth muscle cells.
abstract: Asthma is characterized by an increase in airway smooth muscle mass and a decreased distance between the smooth muscle layer and the epithelium. Furthermore, there is evidence to indicate that airway smooth muscle cells (ASMC) express a wide variety of receptors involved in the immune response. The aims of this study were to examine the expression of CCR3 on ASMC, to compare this expression between asthmatic and nonasthmatic subjects, and to determine the implications of CCR3 expression in the migration of ASMC. We first demonstrated that ASMC constitutively express CCR3 at both mRNA and protein levels. Interestingly, TNF-alpha increases ASMC surface expression of CCR3 from 33 to 74%. Furthermore, using FACS analysis, we found that ASMC CCR3 is expressed to a greater degree in asthmatic vs control subjects (95 vs 75%). Functionality of the receptor was demonstrated by calcium assay; the addition of CCR3 ligand eotaxin to ASMC resulted in an increase in intracellular calcium production. Interestingly, ASMC was seen to demonstrate a positive chemotactic response to eotaxin. Indeed, ASMC significantly migrated toward 100 ng/ml eotaxin (2.2-fold increase, compared with control). In conclusion, the expression of CCR3 by ASMC is increased in asthmatics, and our data show that a CCR3 ligand such as eotaxin induces migration of ASMC in vitro. These results may suggest that eotaxin could be involved in the increased smooth muscle mass observed in asthmatics through the activation of CCR3.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joubert
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lajoie-Kadoch
authors.forename: Isabelle
authors.initials: I
authors.lastname: Labonté
authors.forename: Abdelilah Soussi
authors.initials: AS
authors.lastname: Gounni
authors.forename: Karim
authors.initials: K
authors.lastname: Maghni
authors.forename: Vincent
authors.initials: V
authors.lastname: Wellemans
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Bouchaib
authors.initials: B
authors.lastname: Lamkhioued
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D008024:Ligands; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium