Abstract:
:Phosphoinositide 3-kinase gamma (PI3Kgamma) in neutrophils plays a critical role in the directed migration of these cells into inflamed tissues. In this study, we demonstrate the importance of the endothelial component of PI3Kgamma activity relative to its leukocyte counterpart in supporting neutrophil interactions with the inflamed vessel wall. Despite the reconstitution of class-Ib PI3K function in neutrophils of p110gamma-/- mice, we observed a 45% reduction in accumulation of these cells in an acute lung injury model. Mechanistically, this appears to result from a perturbation in selectin-mediated adhesion as manifested by a 70% reduction in wild-type (WT) neutrophil attachment to and 17-fold increase in rolling velocities on p110gamma-/- microvessels in vivo in response to tumor necrosis factor alpha (TNFalpha). This alteration in adhesion was further augmented by a deficiency in p110delta, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by cytokine-stimulated endothelium. Interestingly, E-selectin-mediated adhesion in p110gamma-/-) mice was impaired by more than 95%, but no defect in nuclear factor kappa B (NF-kappaB)-induced gene expression was observed. These findings suggest a previously unrecognized partnership between class-I PI3Ks expressed in leukocytes and endothelium, the combination of which is required for the efficient trafficking of immunocompetent cells to sites of inflammation.
journal_name
Bloodjournal_title
Bloodauthors
Puri KD,Doggett TA,Huang CY,Douangpanya J,Hayflick JS,Turner M,Penninger J,Diacovo TGdoi
10.1182/blood-2005-01-0023subject
Has Abstractpub_date
2005-07-01 00:00:00pages
150-7issue
1eissn
0006-4971issn
1528-0020pii
2005-01-0023journal_volume
106pub_type
杂志文章相关文献
BLOOD文献大全abstract::Six patients with relapsed hairy cell leukemia after splenectomy were treated with high-dose methotrexate and leucovorin rescue. Five patients had objective responses as determined by improved blood counts. In two of them, the response has continued for more than 14 and 44 months, respectively. Intensive treatment wit...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus-transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood ce...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-05-157974
更新日期:2008-11-15 00:00:00
abstract::The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PA...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Pluripotent hematopoietic stem cells have been studied extensively, but the events that occur during their differentiation remain largely uncharted. To develop a system that allows the differentiation of cultured multipotent progenitors by time-lapse fluorescence microscopy, myelomonocytic cells were labeled with gree...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::In this issue of Blood,Gerber et al use aldehyde dehydrogenase (ALDH) activity to further subdivide the CD34(+)CD38(-) compartment in the bone marrow of acute myeloid leukemia (AML) patients. They identify a unique population with intermediate ALDH activity (ALDH(int)) that contains leukemia stem cells (LSCs). Moreove...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2012-02-406751
更新日期:2012-04-12 00:00:00
abstract::Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library and by polymerase chain reaction (PCR) amplification of human bone marrow and erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that exhibit several unexpected structural properties as compared with the Rh polypep...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-08-15 00:00:00
abstract::Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)-lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte mot...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-05-286872
更新日期:2010-11-25 00:00:00
abstract::Elevated circulatory levels of many blood coagulation factors are known to be a risk factor for deep vein thrombosis in humans. Here we report the first direct demonstration of a close association between elevated circulatory factor IX levels in mice with thrombosis as well as myocardial fibrosis. Transgenic mice over...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1581
更新日期:2003-03-01 00:00:00
abstract::Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations wi...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2000-06-15 00:00:00
abstract::Administration of hematopoietic growth factors is being used increasingly to obtain populations of blood progenitor/stem cells (PBPC) for clinical transplantation. Here we examined the effect of combining stem cell factor (SCF ) and granulocyte colony-stimulating factor (G-CSF ) versus G-CSF alone in a randomized clin...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1997-11-01 00:00:00
abstract::Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-04-780106
更新日期:2017-11-30 00:00:00
abstract::The p21-activated kinases (Paks) are serine/threonine kinases that are major effectors of the Rho guanosine 5'\x{2011}triphosphatase, Rac, and Cdc42. Rac and Cdc42 are known regulators of hematopoietic stem and progenitor cell (HSPC) function, however, a direct role for Paks in HSPCs has yet to be elucidated. Lin(-)Sc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-10-460709
更新日期:2013-03-28 00:00:00
abstract::We previously reported the characterization of human osteoclast-associated receptor (hOSCAR), a novel Fc receptor gamma-chain (FcRgamma)-associated receptor expressed by myeloid cells. Here we show that ligation of hOSCAR by specific antibodies promotes dendritic cell (DC) survival by an extracellular signal-regulated...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-07-2809
更新日期:2005-05-01 00:00:00
abstract::Serum response factor (SRF) is a ubiquitously expressed transcription factor and master regulator of the actin cytoskeleton. We have previously shown that SRF is essential for megakaryocyte maturation and platelet formation and function. Here we elucidate the role of SRF in neutrophils, the primary defense against inf...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-06-507582
更新日期:2014-05-08 00:00:00
abstract::An abnormal von Willebrand factor (vWF) gene restriction pattern has been found in a patient with von Willebrand disease. Because this gene alteration is not present in his parents or in 50 normal and 25 affected subjects, and the restriction fragment length polymorphism haplotypes are inherited normally in the patien...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::To determine if megakaryocytes are targeted by immune thrombocytopenic purpura (ITP) autoantibodies, as are platelets, we have studied the effects of ITP plasma on in vitro megakaryocytopoiesis. Umbilical cord blood mononuclear cells were incubated in the presence of thrombopoietin and 10% plasma from either ITP patie...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-05-1475
更新日期:2003-08-01 00:00:00
abstract::Allogeneic stem cell transplantation (SCT) is curative for hemophagocytic lymphohistiocytosis (HLH). However, patients frequently have significant morbidity before transplantation and there is high transplant-related mortality (TRM). Because first-degree HLH is caused by immune dysregulation, a reduced-intensity condi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-05-1819
更新日期:2006-02-01 00:00:00
abstract::Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in α-granules of platelets and is enriched in hyperactive "ultra-large" VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-03-632901
更新日期:2015-10-01 00:00:00
abstract::Toll-like receptors orchestrate rapid local protective innate-immune responses to invading pathogens and optimize leukocyte priming of subsequent adaptive responses. Paradoxically, systemic excess of the TLR2 ligand, bacterial lipoprotein (BLP), suppresses peripheral inflammatory responses. Here, we demonstrate that t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-08-174698
更新日期:2009-04-30 00:00:00
abstract::Acquired chromosomal anomalies (most commonly translocations) in lymphoma and leukemia usually result in either activation of a quiescent gene (by means of immunoglobulin or T-cell-receptor promotors) and expression of an intact protein product, or creation of a fusion gene encoding a chimeric protein. This review sum...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood.v99.2.409
更新日期:2002-01-15 00:00:00
abstract::Intravital microscopy of the calvarium is the only noninvasive method for high-resolution imaging of the bone marrow (BM) and hematopoietic stem cell (HSC) niches. However, it is unclear if the calvarium is representative of all BM compartments. Using the combination of whole body optical imaging, intravital microscop...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-11-467498
更新日期:2013-09-05 00:00:00
abstract::The most common forms of hereditary persistence of fetal hemoglobin (HPFH) involve large deletions that remove the adult delta and beta genes but leave the paired fetal genes (G gamma and A gamma) intact. The size of these deletions has previously eluded exact definition. Using pulsed-field gel electrophoresis and the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Pain is the leading cause of emergency department visits, hospitalizations, and daily suffering in individuals with sickle cell disease (SCD). The pathologic mechanisms leading to the perception of pain during acute RBC sickling episodes and development of chronic pain remain poorly understood and ineffectively treate...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-327429
更新日期:2011-09-22 00:00:00
abstract::McCullough and colleagues show that problems with cord banking still exist. To improve the results of cord transplantations, more attention should be given to ensuring quality standards rather than just collecting more units. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2009-06-226738
更新日期:2009-08-20 00:00:00
abstract::Cellular interleukin 6 (IL-6) is an important growth factor for Kaposi sarcoma- associated herpesvirus (KSHV)-associated neoplasms, which include human immunodeficiency virus (HIV)-related and -unrelated cases of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Increased ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.2.649
更新日期:2002-01-15 00:00:00
abstract::Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, incl...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-400184
更新日期:2012-08-09 00:00:00
abstract::Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) ...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-09-15 00:00:00
abstract::In this issue of Blood, Rowley et al report that noncoding RNAs precisely regulate the messenger RNA (mRNA) profile in platelets. Interfering in this process using genetically engineered mice affects hemostatic and thrombotic functions of platelets. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2016-01-694893
更新日期:2016-04-07 00:00:00
abstract::Among the most striking morphological features of acute nonlymphoblastic leukemias (ANLL) is the occurrence of eosinophilic cytoplasmic inclusions known as Auer rods on Auer bodies. We examined immature myeloid cells from the peripheral blood of 9 human fetuses of 16-19 wk gestation for the presence of such structures...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer r...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-202507
更新日期:2009-07-16 00:00:00