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CXCL 1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro
Author(s) -
Alkhouri H.,
Moir L. M.,
Armour C. L.,
Hughes J. M.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12224
Subject(s) - chemotaxis , cytokine , immunology , microbiology and biotechnology , in vitro , biology , receptor , chemistry , biochemistry
Summary Background Activated mast cells ( MC ) numbers on airway smooth muscle ( ASM ) are increased in eosinophilic asthma. In vitro , asthmatic cytokine‐stimulated ASM cell‐conditioned medium ( CM ) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM . However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified. Objective To identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis. Methods Confluent, serum‐starved ASM cells from donors with and without asthma were stimulated with IL ‐1β and T‐helper ( T h)1 ( TNF α and IFN γ) or T h2 ( IL ‐4, IL ‐13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT ‐ PCR and inhibitory role investigated in MC chemotaxis and Ca 2+ mobilization assays. Results Only CXCL 1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following T h1 and T h2 cytokine stimulation. CXCL 1 m RNA expression was also increased. Exogenous rh‐ CXCL 1 significantly inhibited MC intracellular Ca 2+ mobilization and chemotaxis to either CXCL 10, CXCL 8 or CM collected from asthmatic ASM cells following T h1 or T h2 cytokine stimulation. Neutralizing CXCL 1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis. Conclusions CXCL 1 was a major factor regulating MC chemotaxis in vitro . Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma. Clinical Relevance CXCL 1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology.