title: Free IL-15 Is More Abundant Than IL-15 Complexed With Soluble IL-15 Receptor-α in Murine Serum: Implications for the Mechanism of IL-15 Secretion.
abstract: IL-15 is a cytokine that is part of the innate immune system, as well as a proposed myokine released from skeletal muscle during physical exercise that mediates many of the positive physiological effects of exercise. Many of the immune functions of IL-15 are mediated by juxtacrine signaling via externalized IL-15 bound to membrane-associated IL-15 receptor-α (IL-15Rα). Serum and plasma samples also contain measurable concentrations of IL-15, believed to arise from proteolytic cleavage of membrane-associated IL-15/IL-15Rα complexes to generate soluble IL-15/IL-15Rα species. Here, we validate commercial assays that can distinguish the free form of IL-15 and IL-15/IL-15Rα complexes. These assays showed that most (86%) IL-15 in mouse serum resides in the free state, with a minor proportion (14%) residing in complex with IL-15Rα. Given the much shorter half-life of free IL-15 compared with IL-15/IL-15Rα complexes, these findings cast doubt on the currently accepted model for IL-15 secretion from cleavage of membrane-bound IL-15/IL-15Rα and suggest that IL-15 is released as a free molecule by an unknown mechanism.
authors.affiliation: Geriatric Research, Education, and Clinical Center (B.G.A., L.S.Q.), and Research Service (L.S.Q.), Veteran's Administration Puget Sound Health Care System, Seattle, Washington 98108; and Division of Gerontology and Geriatric Medicine (B.G.A., L.S.Q.), Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Anderson
authors.affiliation: Geriatric Research, Education, and Clinical Center (B.G.A., L.S.Q.), and Research Service (L.S.Q.), Veteran's Administration Puget Sound Health Care System, Seattle, Washington 98108; and Division of Gerontology and Geriatric Medicine (B.G.A., L.S.Q.), Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: LeBris S
authors.initials: LS
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006207:Half-Life; D019409:Interleukin-15 / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D053647:Receptors, Interleukin-15 / Q000097:blood / Q000276:immunology
chemical_list: C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15