depth-mining-network-with-edge-sensitive-context-for-red-green-blue

Depth-Mining Network with Edge-Sensitive Context for Red-Green-Blue-Depth Surface Defect Segmentation

Red-green-blue-depth (RGB-D) surface defect segmentation combines RGB and depth information to perceive the spatial distribution of defects in complex, ...

Zhengzhou University

Interleukin-16 (IL-16) induces the chemotaxis and activation of mast cells (MCs) and other cell types. While it has been concluded that CD4 is the primary IL-16 receptor on T cells, at least one other IL-16 receptor exists. We now show that the IL-16-responsive human MC line HMC-1 lacks CD4, and that the IL-16-mediated chemotactic and Ca2+ mobilization responses of this cell can be blocked by anti-CD9 monoclonal antibodies (mAbs) but not by mAbs directed against CD4 or other tetraspanins. Anti-CD9 mAbs also inhibited the IL-16-mediated activation of nontransformed human cord blood-derived MCs and mouse bone marrow-derived MCs by 50% to 60%. The chemotactic response of HMC-1 cells to IL-16, as well as the binding of the cytokine to the cell's plasma membrane, was inhibited by CD9-specific antisense oligonucleotides. CD9 is therefore essential for the IL-16-mediated chemotaxis and activation of the HMC-1 cell line. In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants. The ability of wortmannin and xestopongin C to inhibit the IL-16-mediated chemotactic response of these cells suggests that the cytokine activates a phosphatidylinositol 3-kinase (PI3K)/inositol trisphosphate-dependent signaling pathway in MCs. This is the first report of a tetraspanin that plays a prominent role in a cytokine-mediated chemotactic response of human MCs.

Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor.

NF-E2 is a prime regulator of megakaryocyte (MK) terminal differentiation and platelet release. By overexpressing the p45 subunit of NF-E2, we aim to increase the proportion of mature MKs and the potential for platelet production in vitro and in vivo.

NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo.

The development of immune cytopenias is a well-recognized side effect of many drugs. Quinine- and quinidine-dependent antibodies are classic examples of drug-induced effects that cause severe, life-threatening thrombocytopenia. Whereas the effects of drug-dependent antibodies on platelets have been well documented, their effects on megakaryocyte (Mk) biology are still unclear. We analyzed sera from several quinine-induced thrombocytopenia (QITP) patients on highly pure Mks (98% glycoprotein IIb-positive [GPIIb(+)]; 92% GPIX(+)) derived from human CD34(+) cells cultured with human thrombopoietin. We demonstrate by flow cytometry and confocal microscopy that QITP IgGs bind Mks efficiently in the presence of quinine. Incubation of day-4 Mks with QITP sera or purified IgG resulted in induction of apoptosis, a significant decrease in cell viability, and an increase in cell death. Furthermore, QITP sera preferentially reduced the number of late GPIX(+)/GPIbα(+) Mks and the number of receptors per cell in the surviving population. Ploidy distribution, lobularity, and average cell size of Mks remained unchanged after treatment. In addition, treated Mks showed a marked decrease in their proplatelet production capacity, suggesting that drug-dependent antibodies hinder platelet production. Therefore, QITP antibodies considerably reduce the proplatelet production capabilities of Mks despite undetectable effects on DNA content, morphology, and cell size.

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro.

Primary immune thrombocytopenia (ITP) and drug-induced thrombocytopenia (DITP) are disorders caused primarily by the presence of anti-platelet auto-antibodies (Abs). Hematologists have traditionally seen thrombocytopenia as the result of increased destruction of Ab-coated platelets by the reticuloendothelial system. While accurate, this approach does not fully account for other laboratory observations. There is increasing evidence suggesting a significant cellular component in the etiology of both ITP and DITP. In ITP, megakaryocytes (Mks) show characteristics consistent with increased apoptosis, which correlates with a reduction in platelet production capacity. Platelet production by Mks is impaired in both the bone marrow of ITP patients and in Mks produced in vitro when treated with ITP or DITP auto-Abs. Recently, it was shown that anti GPIb/IX DITP Abs act directly on Mks and induce apoptosis, hinder differentiation, and prevent platelet production. The origin of pathological megakaryocytic apoptosis is yet to be explored in more detail but current observations imply that there is a direct contribution by anti-platelet Abs. Here we review the evidence for Ab-mediated megakaryocytic damage in ITP and DITP, examine possible molecular mechanisms and consider potential clinical implications.

A megakaryocyte with no platelets: anti-platelet antibodies, apoptosis, and platelet production.

Primary immune thrombocytopenia is an autoimmune disease mediated by antiplatelet autoantibodies that cause platelet destruction and suppression of platelet production. In vitro effects of autoantibodies on megakaryocyte production and maturation have been reported recently. However, the impact of these autoantibodies on crucial megakaryocyte functions, proplatelet formation and subsequent platelet release, has not been evaluated. We examined the effects of serum and IgG from 19 patients with immune thrombocytopenia using day 8 or 9 megakaryocytes (66.3 ± 10.6% CD41(+)), derived from cord blood hematopoietic stem cells (CD34(+)). The number of proplatelet-bearing megakaryocytes, the number of platelets released in the culture, total megakaryocyte numbers, ploidy pattern and caspase activation were measured at various times after treatment. After 5 days of treatment the number of proplatelet-bearing megakaryocytes was significantly decreased by 13 immune thrombocytopenia autoantibodies relative to the control group (P<0.0001) and this decrease was accompanied by a corresponding reduction of platelet release. Other features, including total megakaryocyte numbers, maturation and apoptosis, were not affected by immune thrombocytopenia antibodies. Treating the megakaryocytes with the thrombopoietin receptor agonists romiplostim and eltrombopag reversed the effect of the autoantibodies on megakaryocytes by restoring their capacity to form proplatelets. We conclude that antiplatelet antibodies in immune thrombocytopenia inhibit proplatelet formation by megakaryocytes and hence the ability of the megakaryocytes to release platelets. Treatment with either romiplostim or eltrombopag regenerates proplatelet formation from the megakaryocytes.

Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro.

Estrogen withdrawal, a characteristic of female aging, is associated with age-related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-α and -β, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17β-estradiol (E2) on GPR30-mediated proliferation and interleukin-1β (IL-1β)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1β-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1β-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors.

Article	Year
Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor. Blood\| PubMed ID: 16144798	2006
NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo. Experimental hematology\| PubMed ID: 17923245	2008
Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro. Blood\| PubMed ID: 21487107	2011
A megakaryocyte with no platelets: anti-platelet antibodies, apoptosis, and platelet production. Platelets\| PubMed ID: 22742725	2013
Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro. Haematologica\| PubMed ID: 25682608	2015
Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc. The Journal of steroid biochemistry and molecular biology\| PubMed ID: 26815911	2016

Feng Yan

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