Adenosine 3',5'-monophosphate-dependent protein kinase of cultured mammalian cells

Protein kinase was partially purified from Chang's liver cells, 3T6 mouse embryo fibroblasts, and HeLa cells. The rate of histone phosphorylation catalyzed by the kinase from each of these cell lines was stimulated two- to three-fold by 1 x 10(-6) molar adenosine 3',5'-monophosphate. The same concentration of guanosine 3',5'-monophosphate failed to stimulate these kinases.     

Impaired prion replication in spleens of mice lacking functional follicular dendritic cells

In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes and in the stroma, which contains follicular dendritic cells (FDCs). Formation and maintenance of mature FDCs require the presence of B cells expressing membrane-bound lymphotoxin-alpha/beta. Treatment of mice with soluble lymphotoxin-beta receptor results in the disappearance of mature FDCs from the spleen. We show that this treatment abolishes splenic prion accumulation and retards neuroinvasion after intraperitoneal scrapie inoculation. These data provide evidence that FDCs are the principal sites for prion replication in the spleen.     

Regulation of bone mass in mice by the lipoxygenase gene Alox15

The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development. Pharmacologic inhibitors of this enzyme improved bone density and strength in two rodent models of osteoporosis. These results suggest that drugs targeting the 12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis.     

Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi Burkitt's lymphoma cells

All human gamma delta T cells coexpressing the products of the variable (V) region T cell receptor (TCR) gene segments V gamma 9 and V delta 2 recognize antigens from mycobacterial extracts and Daudi cells. Exogenous and endogenous ligands on the cell surface, homologous to the groEL heat shock family, induced reactivities that resembled superantigen responses in this major subset of human peripheral blood gamma delta T cells. Stimulation of human V gamma 9/V delta 2 T cells is not restricted by human leukocyte antigens (HLA), including nonpolymorphic beta 2-microglobulin (beta 2M)-associated class Ib molecules. These data may be important for understanding the role of gamma delta T cells in autoimmunity and in responses to microorganisms and tumors.