Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 9, Pages 3333-3338Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0508946103
Keywords
intracellular cytokine receptor; intracellular cytokine trafficking; piecemeal degranulation; vesicular transport
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Funding
- NHLBI NIH HHS [HL70270, R01 HL070270] Funding Source: Medline
- NIAID NIH HHS [R01 AI020241, AI51645, R37 AI020241, R01 AI022571, AI20241, AI22571, R01 AI051645] Funding Source: Medline
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Although leukocytes of the innate immune system, including eosinophils, contain within their granules preformed stores of cytokines available for selective and rapid release, little is known about the mechanisms governing the mobilization and secretion of these cytokines. Here we show that a cytokine receptor, the IL-4 receptor a chain, mediates eotaxin-stimulated mobilization of preformed IL-4 from eosinophil granules into secretory vesicles. Eosinophils contain substantial intracellular quantities of several granule- and vesicle-associated cytokine receptors, including IL-4, IL-6, and IL-13 receptors as well as CCR3. Both IL-4 and IL-4 receptor a chain colocalized in eosinophil granules; and after eotaxin-stimulation, IL-4 receptor a chain, bearing bound IL-4, was mobilized into secretory vesicles. These findings indicate that intracellular cytokine receptors within secretory vesicles transport their cognate cytokines requisite for the secretion of cytokines preformed in innate immune leukocytes.
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