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Human eosinophils prefernentially surivive on tissue fibronectin compared with plasama fibronection
Author(s) -
WALSH G.M,
SYMON F. A.,
WARDLAW A. J.
Publication year - 1995
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/j.1365-2222.1995.tb03260.x
Subject(s) - fibronectin , medicine , immunology , pathology , biology , microbiology and biotechnology , extracellular matrix
Summary Background Eosinphil‐derived inflamatory mediators including cytolines are considered to be important in the pathogenesis of allergic inflammation. Fibronectin (Fn) has been shown to be a physiogical trigger of autocrine cytokihne production by human eosinophils. Fn is encoded by a single gene, but alternate splicing of the primary RNA transcript results in polypeptide diversity in a cell type‐specific fashion. Thus, tissue Fn contains approxmately 50% more of the CS‐1 cell binding region recognized by the integrin α4 β1 compared with lasma Fn. Objective Since eosinophil;s are predominantly tissue‐dwelling cells we compared the effect of tissue and plasama Fn on eosinophil surivivial in culture. Methods The viability and vytokine generation of eosinophils (>99.9%) pure) cultured for up to 4 days in 96 well plates coated with tissue Fn. Plasama Fn or BSA was compared. Results There was a deingficant difference in the ablity if tissue Fn to support eosinophil survival com‐pared with plasma Fn (P <0.001). Optimal survivial with tissue Fin was seen at 25 μ. w4ell (70% ‐ + 2.0%) viability at 3 days vs 7% ‐ + 2.2 % viability on BSA). Significant (p <0.001) cell viability on tissue Fn was observed for up to 4 days in culture (54% ‐ + compared with BSa coated wells. Addition of autologous mononuclear cells (final concentration 0.5%, 1% or 2%) resulted in plasama Fndependent eosinophil surivival comparable to that 99.9% pure eosinophils adhreent to tissue Fn. Tissue Fn‐dependent survival was significantly inhibited by anti‐interleukin‐3, anti‐granulocyte macrophage colony stimulating factor (gm‐csf) and anti ‐Il‐5 monoclonal antibodies. Picogram quantities of these three cytokins were detected in supernatants from eosinophils cultured for 3 days on tissue Fn was significantly inhibited by anti‐31 and α4 β monoclonal antibody (MoAb) and also by MoAB specific for the Cs‐1 motif in the IIICS region of fn. Conclusion These observations show preferential survival of eosinophils cultured on tissue Fn as a result of α4 β‐dependent interaction with the CS‐1 region of tissue Fn triggering autocrine cytokine synthesis and release,thereby promoting their survival and presistence within the tissues.