title: Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: a possible biochemical mechanism for allergic eosinophilic inflammation of the airways.
abstract: We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted in exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted in a significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1 cells was mediated through the CRTH2 receptor. Cell migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC-ε, PKC-δ, and PKA-α, -γ, and -IIαreg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils.
authors.affiliation: Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Liege University Hospital (Centre Hospitalier Universaitaire-C.H.U.), 4000 Liege, Belgium. amrel_shazly@hotmail.com
authors.forename: Amr E
authors.initials: AE
authors.lastname: El-Shazly
authors.forename: Dominique Y
authors.initials: DY
authors.lastname: Begon
authors.forename: Gaelle
authors.initials: G
authors.lastname: Kustermans
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arafa
authors.forename: Estelle
authors.initials: E
authors.lastname: Dortu
authors.forename: Monique
authors.initials: M
authors.lastname: Henket
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Lefebvre
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000378:metabolism / Q000473:pathology*; D004804:Eosinophils / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000378:metabolism / Q000473:pathology*; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014660:Vasoactive Intestinal Peptide; C036293:prostaglandin D2 receptor