Expression of IL-5 alters bone metabolism and induces ossification of the spleen in transgenic mice

We have developed a transgenic mouse line, NJ.1638, which expresses high le vels of IL-5 from T cells, with profound hematological consequences. Eosino phils comprise more than 60% of circulating white blood cells in these anim als, with the total peripheral white blood cell counts increasing more than 40-fold relative to wild-type littermates. This extraordinary proliferativ e capacity is sustained by expanded sites of extramedullary hematopoiesis a nd is accompanied by multifocal, ectopic bone formation in the spleen. Hist ology of the splenic nodules revealed the presence of osteoid matrices and osteocytes trapped within mineralized trabecular plates. In addition, polar ized light microscopy of calcified tissue sections revealed both woven bone and areas of organized lamellar bone. Morphometric assessments demonstrate d that both the growth and mineralization of splenic bone occurred at rates nearly an order of magnitude higher than in skeletal bone. Skeletal bone m etabolic parameters were also perturbed. We also observed heterotopic ossif ication of the spleen and perturbation of skeletal bone homeostasis followi ng adoptive engraftment of transgenic marrow to wild-type recipients. These data suggest that IL-5 overexpression mediates bone formation through the mobilization of marrow-derived osteogenic progenitors and/or the inhibition of recruited osteoclasts.