Dexamethasone (DEX) is a potent immunosuppressive agent used in the treatment of several disorders. However, despite its beneficial effects, DEX puts patients at risk for opportunistic infections, especially pulmonary aspergillosis. Previously we reported that in vitro granulocyte-macrophage colony-stimulating factor (GM-CSF) blocks the immunosuppressive action of DEX on bronchoalveolar macroph...

Sublethally irradiated mice were administered with scorpion venom peptides (SVP) or with PBS in the saline control group, 3 days before and 7 consecutive days after irradiation. Hematopoietic recovery was assessed by bone marrow (BM) cell proliferation index (PI) and colony forming unit-granulocyte/macrophage (CFU-GM), spleen weight index (SI) and thymus weight index (TI), colony-forming unit-s...

Bone marrow (BM) transplantation still must overcome multiple difficulties and should benefit from better understanding of stem-cell homing and mobilization. Here, we analyzed the involvement of several adhesion molecules in the two processes by treating mice with monoclonal antibodies against these molecules. Treatment of lethally irradiated mice grafted with isogeneic BM cells showed that at ...

Apolipoprotein E (apoE) influences both innate and acquired immunity in cultured cells. To determine whether apoE affects the immune system in vivo, Listeria monocytogenes (LM) was administered intraperitoneally (10(4) c.f.u.) to congenic C57BL/6 apoE-/- and +/+ mice (n = 12 in each group). Survival was assessed daily for 5 days. Deficiency of apoE significantly increased death by day 5 (P = 0....

The degree of redundancy between thrombopoietin (Tpo) and steel factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors. Double-mutant c-Mpl(-/-)Kit(Wv/Wv) mice exhibited reduced viability, making up only 2% of the offspring from c-Mpl(-/-)Kit(Wv/)(+) intercrosses. The thrombocytopenia and megak...

The bone marrow of the adult mouse contains stem cells that continuously replenish the myeloid and lymphoid systems (1-4). The best characterized of these stem cells is that which differentiates into myeloid cells, i.e., erythrocytes, granulocytes, and megakaryocytes. This cell can easily be measured by its ability to form macroscopic colonies in the spleens of irradiated mice (5). Using radiat...

The effects of partially purified thrombopoietin (TPO). prepared from the plasma of thrombocytopenic rabbits, upon megakaryocyte colony-forming cells (Meg-CFC), megakaryocytes, and platelets were evaluated. The thrombopoiesis-stimulating activity of both types of preparations of TPO used was established by their ability to increase the levels of selenomethionine-75Se (75SeM) in the circulating ...

Fatty acid epoxides are important lipid signaling molecules involved in the regulation of vascular tone and homeostasis. Tissue and plasma levels of these mediators are determined by the activity of cytochrome P450 epoxygenases and the soluble epoxide hydrolase (sEH), and targeting the latter is an effective way of manipulating epoxide levels in vivo. We investigated the role of the sEH in regu...

Acquired mutations in KIT are driver mutations in systemic mastocytosis (SM). Here, we tested the role of SHP2/PTPN11 phosphatase in oncogenic KIT signaling using an aggressive SM mouse model. Stable knock-down (KD) of SHP2 led to impaired growth, colony formation, and increased rates of apoptosis in P815 cells. This correlated with defects in signaling to ERK/Bim, Btk, Lyn, and Stat5 pathways ...

Efficient transfer of the beta-globin gene into primitive hematopoietic progenitors was achieved with consistent and significant expression in the progeny of those cells. Retroviral vectors containing the intact genomic human beta-globin gene and the neomycin (G418)-resistance (neoR) gene were constructed. These gave titers of 10(6) or more neoR colony-forming units/ml when packaged in psi 2 ce...