Natural Killer Cells, Bone, and the Bone Marrow: Studies in Estrogen-Treated Mice and in Congenitally Osteopetrotic (mi/mi) Mice

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Abstract
Mice lose natural killer cells after 6 weeks of treatment with 17β-estradiol. We here demonstrate that the same protocol leads to loss of genetic resistance to bone marrow transplantation and to significant osteoproliferation with loss of bone marrow. We also show that mice with reduced marrow because of congenital osteopetrosis are deficient in natural killing. These findings are consistent with previous evidence that natural killing and genetic resistance to bone marrow transplantation are dependent upon the marrow. Temporal studies of bone histology and radiology during and after treatment with estrogen reveal that alterations in natural killing proceed more rapidly than changes in bone marrow volume. These studies also demonstrate that estrogens induce osteoproliferation only at endosteal surfaces that are adjacent to hematopoietic marrow. From these observations, we conclude that estrogens do not reduce natural killer cells simply by reducing the volume of bone marrow. Estrogens may instead have an effect on bone marrow cells that leads both to osteoproliferation and to a deficiency of marrow-dependent cells.