{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:34:47Z","timestamp":1740144887811,"version":"3.37.3"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[1992,8,1]],"date-time":"1992-08-01T00:00:00Z","timestamp":712627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007197","name":"USPHS","doi-asserted-by":"crossref","award":["DE 06065"],"award-info":[{"award-number":["DE 06065"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1992,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent studies have provided evidence that cells of the immune system and their associated cytokines function in the regulation of bone turnover. The incisors absent (ia) osteopetrotic rat represents a model in which a defect in the immune system and bone resorption can be studied. Osteopetrosis in the ia rat is characterized by a generalized excess accumulation of bone as a result of reduced bone resorption by defective osteoclasts that lack a ruffled border and the ability to exocytose their osteolytic enzymes. Previous attempts to identify associated defects in the ia immune system have proven unsuccessful; ia rats demonstrate normal delayed hypersensitivity, mitogenic activity, and macrophage function. Inasmuch as the skeletal manifestations of the ia mutation may be the result of a defect in exocytosis, related defects may be evident in immune cells utilizing exocytosis of granules or enzymes for their cytolytic function. Natural killer (NK) cells function by such a mechanism. Therefore, these studies were undertaken to evaluate the natural immune system in ia rats. NK activity assessed by 51Cr release assays was significantly reduced in ia animals compared to normal littermates. Mononuclear cells isolated from the peripheral blood of ia rats revealed a significantly greater percentage of large granular lymphocytes than normal littermates. Comparison of NK cell phenotypes using two phenotypic parameters for NK cells (OX8+, OX 19\u2212 cells and 3.2.3+ cells) revealed that the mononuclear isolates of spleen and peripheral blood of mutant animals had significantly greater percentages of OX8+, OX 19\u2212 and 3.2.3+ cells than normal controls. Levels of BLT esterase (BLTE), a serine protease associated with the cytolytic mechanism of NK cells, were found to be greater in unsorted ia mononuclear cells than in normal cells but were equivalent in normal and mutant 3.2.3+ cells isolated by fluorescence-activated cell sorting. BLTE activity was enhanced but equal in normal and mutant 3.2.3+ cells stimulated with IL-2. The 3.2.3+ NK isolates demonstrated equal lytic activity in ia and normals, but when normal or mutant 3.2.3\u2212 cells (non-NK cells) were added to the 3.2.3+ia cells the lytic activity was significantly reduced. 3.2.3\u2212 cells had no effect on the activity of 3.2.3+ normal cells. The results indicate that 3.2.3+ mutant NK cells have normal lytic activity and BLTE activity and can respond to IL-2. The NK cells in the mutant are suppressed by a non-NK mononuclear cell, resulting in the lytic defect. A known suppressor of NK cells, prostaglandin, does not appear to be responsible for the NK defect in this mutant, because indomethacin, an inhibitor of prostaglandin synthesis, did not correct the defect.<\/jats:p>","DOI":"10.1002\/jbmr.5650070811","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T17:09:02Z","timestamp":1265216942000},"page":"941-949","source":"Crossref","is-referenced-by-count":7,"title":["Qualitative defects in natural killer cell function in <i>ia<\/i> osteopetrotic rats"],"prefix":"10.1093","volume":"7","author":[{"given":"Gary B.","family":"Schneider","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Loyola University, Stritch School of Medicine, Maywood, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Relfson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Loyola University, Stritch School of Medicine, Maywood, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Section of Hematology\/Oncology, Loyola University, Stritch School of Medicine, Maywood, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1992,8,1]]},"reference":[{"key":"2024013113112427300_bib1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/00003086-198410000-00026","article-title":"Congenital osteopetrotic mutations as probes of the origin, structure, and function of osteoclasts.","volume":"189","author":"Marks","year":"1984","journal-title":"Clin Orthop"},{"key":"2024013113112427300_bib2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/aja.1001380204","article-title":"Pathogenesis of osteopetrosis of the ia rat: Reduced bone resorption due to reduced osteoclast function.","volume":"138","author":"Marks","year":"1973","journal-title":"Am J Anat"},{"key":"2024013113112427300_bib3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/aja.1001510110","article-title":"Studies of the mechanism of spleen cell cure for osteopetrosis in ia rats: Appearance of osteoclasts with ruffled borders.","volume":"151","author":"Marks","year":"1978","journal-title":"Am J Anat"},{"key":"2024013113112427300_bib4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1073\/pnas.74.1.339","article-title":"Immunological defect and its correction in the osteopetrotic mutant rat.","volume":"74","author":"Milhaud","year":"1977","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113112427300_bib5","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-3083.1981.tb00601.x","article-title":"Bone absorption and the immune system.","volume":"14","author":"Nisbet","year":"1981","journal-title":"Scand J Immunol"},{"key":"2024013113112427300_bib6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/aja.1001530209","article-title":"The role of lymphoid cells in bone resorption: Cellular immunological competence in ia rats.","volume":"153","author":"Schneider","year":"1978","journal-title":"Am J Anat"},{"key":"2024013113112427300_bib7","first-page":"391","article-title":"Phagocytosis and acid phosphatase activity of the phagocytic cells in the ia (osteopetrotic) rat.","volume":"30","author":"Schneider","year":"1981","journal-title":"J Reticuloendothel Soc"},{"key":"2024013113112427300_bib8","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0171-2985(84)80003-0","article-title":"Immunological competence in osteopetrotic (ia) rats.","volume":"167","author":"Schneider","year":"1984","journal-title":"Immunobiology"},{"key":"2024013113112427300_bib9","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.4049\/jimmunol.122.6.2541","article-title":"Natural killer 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