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Lipopolysaccharide-Stimulated or Granulocyte-Macrophage Colony-Stimulating Factor-Stimulated Monocytes Rapidly Express Biologically Active IL-15 on Their Cell Surface Independent of New Protein Synthesis^{1 ,2}

Graham G. Neely^*, Stephen M. Robbins^,, Ernest K. Amankwah, Slava Epelman, Howard Wong^¶, Jason C. L. Spurrell, Kiran K. Jandu, Weibin Zhu, Darin K. Fogg, Christopher B. Brown^,|| and Christopher H. Mody^3,,#

Departments of ^* Medical Sciences, Oncology, Biochemistry and Molecular Biology, Microbiology and Infectious Diseases, ^¶ Molecular Pathology, ^|| Medicine, and ^# Internal Medicine, University of Calgary, Calgary, Alberta, Canada

Although IL-15 shares many of the biological activities of IL-2, IL-2 expression is primarily under transcriptional regulation, while the mechanisms involved in the regulation of IL-15 are complex and not completely understood. In the current study, we found that CD14⁺ monocytes constitutively exhibit both IL-15 mRNA and protein. IL-15 protein was found stored intracellularly and stimulation of CD14⁺ monocytes with either LPS or GM-CSF resulted in mobilization of IL-15 stores to the plasma membrane. This rapidly induced surface expression was the result of a translocation of preformed stores, confirming that posttranslational regulatory stages limit IL-15, because it was not accompanied by an increase in IL-15 mRNA and occurred independent of de novo protein synthesis. After fixation, activated monocytes, but not resting monocytes, were found to support T cell proliferation, and this effect was abrogated by the addition of an IL-15-neutralizing Ab. The presence of preformed IL-15 stores and the ability of stimulated monocytes to mobilize these stores to their surface in an active form is a novel mechanism of regulation for IL-15.

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