Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells

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 Fc epsilon RI 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 alpha v). 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.