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Coexistence of reduced function of natural killer cells and osteoclasts in two distinct osteopetrotic mutations in the rat
Author(s) -
Popoff Steven N.,
Jackson Mary E.,
Koevary Steven B.,
Marks Sandy C.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650060308
Subject(s) - osteopetrosis , osteoclast , immune system , bone resorption , natural killer cell , biology , flow cytometry , peripheral blood mononuclear cell , cell , microbiology and biotechnology , mutant , immunology , cytotoxicity , endocrinology , genetics , gene , receptor , in vitro
Recent evidence suggesting that immune cells and their products (cytokines) play an important role in the regulation of skeletal development and function, particularly of the osteoclast, implies that immune cell dysfunction may be involved in the pathogenesis of certain skeletal disorders. The mammalian osteopetroses are a pathogenetically heterogeneous group of skeletal disorders characterized by skeletal sclerosis resulting from reduced osteoclast‐mediated bone resorption. Using a 51 Cr‐release microcytotoxicity assay we demonstrated that splenic natural killer (NK) cell activity was significantly reduced in two distinctly different osteopetrotic mutations in the rat, osteopetrosis ( op ) and toothless ( tl ). To determine whether this reduction in NK cell‐mediated cytotoxicity is caused by decreased cell number and/or function in these osteopetrotic mutants, we quantitated NK cells by analyzing mononuclear cell suspensions labeled for two‐color fluorescence with OX8 and OX 19 monoclonal antibodies in a fluorescence‐activated cell sorter. Flow cytometry of these double‐labeled cells revealed that the percentage of NK cells (OX8 + /OX19 − subset) in op and tl spleens was not significantly different from that of normal spleens. These results suggest that NK cells in these osteopetrotic mutants are functionally defective. Thus aberrations in osteoclast and NK cell function coexist in these mutations, and their developmental relationships deserve further study.