title: Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells.
abstract: Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and FcepsilonRI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN(-/-)) and -sufficient (OPN(+/+)) mice without significant differences in yield, purity, granularity, and viability. Using OPN(-/-) FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin alphav). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN(-/-) mice compared with OPN(+/+) mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions.
authors.affiliation: Department of Dermatology, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Yamanashi, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nagasaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsue
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsushima
authors.forename: Rui
authors.initials: R
authors.lastname: Aoki
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naotomo
authors.initials: N
authors.lastname: Kambe
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimada
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D005333:Fetus; D007073:Immunoglobulin E / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C506896:Spp1 protein, mouse; D053495:Osteopontin; D007073:Immunoglobulin E