The cross sections of the 169 Tm(α,γ) 173 Lu and 169 Tm(α,n) 172 Lu reactions have been measured first time using a new method, by detecting the characteristic X-ray radiation following the electron capture-decay of 172,173 Lu. Despite the relatively long half-life of the reaction products (T 1/2 = 500 and 6.7 days, respectively) it was possible to measure the cross section of the 169 Tm(α,γ) 173 Lu reaction close to the Gamow window (T 9 = 3.5 GK), between E c.m. = 13.16 and 17.08 MeV. The 169 Tm(α,n) 172 Lu reaction cross section was measured from E c.m. = 11.21 MeV up to E c.m. = 17.08 MeV. The experimental results have been compared to theoretical predictions.

β2-integrins of neutrophils play a critical role in innate immune defense but they also participate in tissue destruction during autoimmune inflammation. p190RhoGAP, a regulator of Rho-family small GTPases, is required for integrin signal transduction in fibroblasts. Prior studies have also suggested a role for p190RhoGAP in β2 integrin signaling in neutrophils. To directly test that possibility, we have generated a novel targeted mutation completely disrupting the p190RhoGAP-encoding gene in mice. p190RhoGAP deficiency led to perinatal lethality and defective neural development, precluding the analysis of neutrophil functions in adult p190RhoGAP−/− animals. This was overcome by transplantation of fetal liver cells from p190RhoGAP−/− fetuses into lethally irradiated wild type recipients. Neutrophils from such p190RhoGAP−/− bone marrow chimeras developed normally and expressed normal levels of various cell surface receptors. Though p190RhoGAP−/− neutrophils showed moderate reduction of β2 integrin-mediated adherent activation, they showed mostly normal migration in β2-integrin-dependent in vitro and in vivo assays and normal β2 integrin-mediated killing of serum-opsonized S. aureus and E. coli. A neutrophil- and β2 integrin-dependent transgenic model of the effector phase of autoimmune arthritis also proceeded normally in p190RhoGAP−/− bone marrow chimeras. In contrast, all the above responses were completely blocked in CD18−/− neutrophils or CD18−/− bone marrow chimeras. These results suggest that p190RhoGAP likely does not play a major indispensable role in β2 integrin-mediated in vitro and in vivo neutrophil functions or the effector phase of experimental autoimmune arthritis.

No abstract

BackgroundOsteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2−/−) mice.Materials and methodsThe trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures.ResultsPLCγ2−/− mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLCγ2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLCγ2−/− mice was similar to, or even more robust than, that in wild-type animals.ConclusionsOur results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency–induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis.