Inhibitory effects of a cationic liposome on allergic reaction mediated by mast cell activation

Several studies have shown that cationic liposomes exert immunomodulatory effects with low immunogenicity and toxicity, and offer advantages such as easy preparation and targeting. Cationic liposomes not only transport DNA to immune cells but also enhance the function of antigen presenting cells suc...

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Veröffentlicht in:Biochemical pharmacology 2013-12, Vol.86 (12), p.1731-1738
Hauptverfasser: Inoh, Yoshikazu, Tadokoro, Satoshi, Tanabe, Hiroki, Inoue, Makoto, Hirashima, Naohide, Nakanishi, Mamoru, Furuno, Tadahide
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Sprache:eng
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Zusammenfassung:Several studies have shown that cationic liposomes exert immunomodulatory effects with low immunogenicity and toxicity, and offer advantages such as easy preparation and targeting. Cationic liposomes not only transport DNA to immune cells but also enhance the function of antigen presenting cells such as dendritic cells and macrophages. Here, we investigated the effect of a particular cationic liposome on mast cell function during allergic reaction. We found that the cationic liposomes bound to the mast cell surface suppressed degranulation induced by cross-linking of high affinity immunoglobulin E receptors in a time- and dose-dependent manner. The suppression of degranulation was mediated by impairment of the sustained level of intracellular Ca2+ concentration ([Ca2+]i) derived from the inhibition of store-operated Ca2+ entry. The decrease in sustained elevation of [Ca2+]i led to the suppression of phosphorylation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins such as SNAP-23, syntaxin-4, which are necessary for membrane fusion between secretory granules and the plasma membrane during degranulation. Furthermore, the cationic liposomes suppressed vascular permeability elevation induced by mast cell activation in mice. These results showed that cationic liposomes possess the novel property of inhibiting mast cell activation, suggesting the possibility of developing cationic liposomes as anti-allergic effectors.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2013.09.023