Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils: A possible biochemical mechanism for allergic eosinophilic inflammation of the airways

ArticleinJournal of Biological Chemistry 288(2) · November 2012with13 Reads
DOI: 10.1074/jbc.M112.422675 · Source: PubMed
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 eosinophils cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted into exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted into 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 eosinophils chemotaxis from AR patients and Eol-1 cells, was mediated through CRTH2 receptor. Cells migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition, but not to tyrosine kinase or P38 MAP-kinase 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 IIα reg 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.
    • "Either infection-elicited or oxLDL-driven MCP1, for instance, besides its known CCR2-driven chemotactic function, appear as a key activator of lipid body biogenic and leukotriene synthesizing machineries within macrophagic cells (Pacheco et al., 2007; Silva et al., 2009). Once more specifically regarding eosinophils, synergistic effects on eliciting eosinophil chemotaxis have been also described between PGD2 and at least the cytokines IFN-γ and TNF-α (El-Shazly et al., 2011), as well as, between DP2 activation and vasoactive intestinal peptide VIP (El-Shazly et al., 2013). Moreover, RANTES, IL-16 and MIF are also proteic mediators capable of activating eicosanoid synthesizing machinery within eosinophils culminating with the generation of LTC4 and PGD2, that in turn intracrinally or autocrinally mediate eosinophil secretory functions (Bandeira-Melo et al., 2002b,c; Vieira-de-Abreu et al., 2011). "
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