English Journal

The granzyme B-Serpinb9 axis controls the fate of lymphocytes after lysosomal stress.

Bird CH1, Christensen ME2, Mangan MS1, Prakash MD1, Sedelies KA3, Smyth MJ3, Harper I4, Waterhouse NJ2, Bird PI1.Author information 1Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, VIC, Australia.2Apoptosis and Cytotoxicity Laboratory, Mater Medical Research Institute, Brisbane, QLD, Australia.3Cancer Cell Death, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.4Monash Micro Imaging, Monash University, Melbourne, VIC, Australia.AbstractCytotoxic lymphocytes (CLs) contain lysosome-related organelles (LROs) that perform the normal degradative functions of the lysosome, in addition to storage and release of powerful cytotoxins employed to kill virally infected or abnormal cells. Among these cytotoxins is granzyme B (GrB), a protease that has also been implicated in activation (restimulation)-induced cell death of natural killer (NK) and T cells, but the underlying mechanism and its regulation are unclear. Here we show that restimulation of previously activated human or mouse lymphocytes induces lysosomal membrane permeabilisation (LMP), followed by GrB release from LROs into the CL cytosol. The model lysosomal stressors sphingosine and Leu-Leu-methyl-ester, and CLs from gene-targeted mice were used to show that LMP releases GrB in both a time- and concentration-dependent manner, and that the liberated GrB is responsible for cell death. The endogenous GrB inhibitor Serpinb9 (Sb9) protects CLs against LMP-induced death but is decreasingly effective as the extent of LMP increases. We also used these model stressors to show that GrB is the major effector of LMP-mediated death in T cells, but that in NK cells additional effectors are released, making GrB redundant. We found that limited LMP and GrB release occurs constitutively in proliferating lymphocytes and in NK cells engaged with targets in vitro. In Ectromelia virus-infected lymph nodes, working NK cells lacking Sb9 are more susceptible to GrB-mediated death. Taken together, these data show that a basal level of LMP occurs in proliferating and activated lymphocytes, and is increased on restimulation. LMP releases GrB from LROs into the lymphocyte cytoplasm and its ensuing interaction with Sb9 dictates whether or not the cell survives. The GrB-Sb9 nexus may therefore represent an additional mechanism of limiting lymphocyte lifespan and populations.Cell Death and Differentiation advance online publication, 31 January 2014; doi:10.1038/cdd.2014.7.
Cell death and differentiation.Cell Death Differ.2014 Jan 31. doi: 10.1038/cdd.2014.7. [Epub ahead of print]
Cytotoxic lymphocytes (CLs) contain lysosome-related organelles (LROs) that perform the normal degradative functions of the lysosome, in addition to storage and release of powerful cytotoxins employed to kill virally infected or abnormal cells. Among these cytotoxins is granzyme B (GrB), a protease
PMID 24488096

Genome Sequence of WAU86/88-1, a New Variant of Vaccinia Virus Lister Strain from Poland.

Mavian C, López-Bueno A, Alcamí A.Author information Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Campus de Cantoblanco, Madrid, Spain.AbstractThe poxviruses Warsaw Agricultural University 86 (WAU86) and 88-1 (WAU88-1) were isolated in 1986 to 1988 from separate outbreaks in laboratory mice in Poland and described as ectromelia virus isolates. The genome sequences of these poxviruses reveal that they are almost identical and represent a novel variant of the vaccinia virus Lister strain.
Genome announcements.Genome Announc.2014 Jan 9;2(1). pii: e01086-13. doi: 10.1128/genomeA.01086-13.
The poxviruses Warsaw Agricultural University 86 (WAU86) and 88-1 (WAU88-1) were isolated in 1986 to 1988 from separate outbreaks in laboratory mice in Poland and described as ectromelia virus isolates. The genome sequences of these poxviruses reveal that they are almost identical and represent a no
PMID 24407630

Crosstalk between autophagy and apoptosis in RAW 264.7 macrophages infected with ectromelia orthopoxvirus.

Martyniszyn L, Szulc-Dąbrowska L, Boratyńska-Jasińska A, Struzik J, Winnicka A, Niemiałtowski M.Author information 1 Division of Immunology, Department of Preclinical Sciences, Warsaw University of Life Sciences SGGW (WULS-SGGW) , Warsaw, Poland .AbstractSeveral studies have provided evidence that complex relationships between autophagic and apoptotic cell death pathways occur in cancer and virus-infected cells. Previously, we demonstrated that infection of macrophages with Moscow strain of ectromelia virus (ECTV-MOS) induces apoptosis under in vitro and in vivo conditions. Here, we found that autophagy was induced in RAW 264.7 cells during infection with ECTV-MOS. Silencing of beclin 1, an autophagy-related gene, reduced the percentage of late apoptotic cells in virus-infected RAW 264.7 macrophages. Pharmacological modulation of autophagy by wortmannin (inhibitor) or rapamycin (inductor) did not affect or cause increased apoptosis in ECTV-MOS-infected RAW 264.7 cells, respectively. Meantime, blocking apoptosis by a pan-caspase inhibitor, Z-VAD-FMK, increased the formation of autophagosomes in infected macrophages. Taken together, three important points arise from our study. First, autophagy may co-occur with apoptosis in RAW 264.7 cells exposed to ECTV-MOS. Second, at later stages of infection, autophagy may partially participate in the execution of macrophage cell death by enhancing apoptosis. Third, when apoptosis is blocked infected macrophages undergo increased autophagy. Our results provide new information about the relationship between autophagy and apoptosis in ECTV-MOS-infected macrophages.
Viral immunology.Viral Immunol.2013 Oct;26(5):322-35. doi: 10.1089/vim.2013.0003.
Several studies have provided evidence that complex relationships between autophagic and apoptotic cell death pathways occur in cancer and virus-infected cells. Previously, we demonstrated that infection of macrophages with Moscow strain of ectromelia virus (ECTV-MOS) induces apoptosis under in vitr
PMID 24116707

Japanese Journal

Using polymerase chain reaction for rapid sex-determination of a case of sirenomelia

Acta paediatrica Japonica 40(3), 282-285, 1998-06-01
NAID 10009614940

痕跡的腎臓,尿管,膀胱を有する二足合脚体の1例

先天異常 : 日本先天異常学会会報 : official journal of Congeital Anomalies Research Association of Japan 16(2), 97-103, 1976-06-30
NAID 110002728723

合脚体の1例

先天異常 : 日本先天異常学会会報 : official journal of Congeital Anomalies Research Association of Japan 15(4), 229, 1975-12-30
NAID 110002728662

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