Abstract:
:Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a tyrosine phosphoprotein highly expressed on endothelial cells and leukocytes, is an important component in the regulation of neutrophil transendothelial migration. Engagement of endothelial PECAM-1 activates tyrosine phosphorylation events and evokes prolonged calcium transients, while homophilic engagement of neutrophil PECAM-1 activates leukocyte beta-integrins. Although PECAM-1 modulates polymorphoneutrophil transmigration via homophilic PECAM-1-PECAM-1 interaction, the mechanisms underlying endothelial PECAM-1 function are unknown. Proposed mechanisms include (1) formation of a haptotactic gradient that "guides" neutrophils to the cell-cell border, (2) service as a "passive ligand" for neutrophil PECAM-1, ultimately mediating activation of neutrophil beta integrins, (3) regulation of endothelial calcium influx, and (4) mediation of SH2 protein association, and/or (5) catenin and non-SH2 protein interaction. Utilizing PECAM-1-null "model" endothelial cells (REN cells), we developed a neutrophil transmigration system to study PECAM-1 mutations that specifically disrupt PECAM-1-dependent signaling and/or PECAM-1 cell localization. We report that interleukin-1 beta (IL-1 beta) elicits PECAM-1-dependent transmigration that requires homophilic PECAM-PECAM-1 engagement, but not heterophilic neutrophil PECAM-1 interactions, and is intercellular adhesion molecule-1 dependent. Conversely, whereas IL-8 and leukotriene-B(4)-mediated transmigration is PECAM-1-independent, PECAM-1 and IL-8-dependent transmigration represent separable and additive components of cytokine-induced transmigration. Surprisingly, neither monolayer PECAM-1-regulated calcium signaling, cell border localization, nor the PECAM-1 cytoplasmic domain was required for monolayer PECAM-1 regulation of neutrophil transmigration. We conclude that monolayer (endothelial cell) PECAM-1 functions as a passive homophilic ligand for neutrophil PECAM-1, which after engagement leads to neutrophil signal transduction, integrin activation, and ultimately transmigration in a stimulus-specific manner.
journal_name
Bloodjournal_title
Bloodauthors
O'Brien CD,Lim P,Sun J,Albelda SMdoi
10.1182/blood-2002-08-2396subject
Has Abstractpub_date
2003-04-01 00:00:00pages
2816-25issue
7eissn
0006-4971issn
1528-0020pii
2002-08-2396journal_volume
101pub_type
杂志文章相关文献
BLOOD文献大全abstract::Large granular lymphocytes (LGL) are defined as nonadherent mononuclear cells with cytoplasmic azurophilic granules, avid receptors for the Fc portion of IgG, and cytotoxic functions (NK or ADCC activities). In the present study, the granules of LGL isolated from human peripheral blood have been analyzed by enzyme cyt...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::The CCAAT/enhancer binding protein-alpha (C/EBPalpha) is a transcription factor required for differentiation of myeloid progenitors. In addition to specific DNA binding, C/EBPalpha is also involved in protein-protein interactions, some of which (p21, Cdk2/Cdk4, E2F) appear to be required for inhibition of proliferatio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-02-0477
更新日期:2003-08-15 00:00:00
abstract::We examined the prevalence and prognostic relevance of bone marrow reticulin fibrosis in 526 patients with World Health Organization-defined polycythemia vera evaluated at the time of initial diagnosis. Seventy-four patients (14%) displayed mostly grade 1 reticulin fibrosis, with only 2 cases showing higher-grade fibr...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-11-393819
更新日期:2012-03-08 00:00:00
abstract::The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR),...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1989-03-01 00:00:00
abstract::The dendritic cell (DC)-specific molecule DC-SIGN is a receptor for the HIV-1 envelope glycoprotein gp120 and is essential for the dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and lymph nodes. To identify a DC-SIGN(+) DC in blood that may b...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2001-12-0179
更新日期:2002-09-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) is considered a negative regulator of inflammation, as inhibition of STAT3 signaling enhances antitumor immunity. However, STAT3 activation is a key oncogenic pathway in natural killer (NK)-lineage large granular lymphomas, and we recently reported enhanced pr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-499707
更新日期:2014-07-17 00:00:00
abstract::For most children who relapse with acute lymphoblastic leukemia (ALL), the prognosis is poor, and there is a need for novel therapies to improve outcome. We screened samples from children with B-lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (www.clinicaltrials.gov, #NCT00114348) for somatic mutations ac...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-04-531871
更新日期:2014-11-27 00:00:00
abstract::The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-06-01 00:00:00
abstract::Fanconi anemia (FA) is an autosomal recessive disease marked by developmental defects, bone marrow failure, and cancer susceptibility. FA cells are hypersensitive to DNA cross-linking and alkylating agents and accumulate in the G2 phase of the cell cycle in response to these agents. FA cells also display genomic insta...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::We have investigated the structure of the Ig heavy (IGH) chain locus in 309 cases of acute leukemia. Seventy-one cases of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) were analyzed: in six cases deletion of joining (JH) segments in the presence of cytogenetically normal chromosome 14 was observed. Similar...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::In primary human T cells, anergy induction results in enhanced p59Fyn activity. Because Fyn is the kinase primarily responsible for the phosphorylation of PAG (the phosphoprotein associated with glycosphingolipid-enriched microdomains), which negatively regulates Src-kinase activity by recruiting Csk (the C-terminal S...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-07-038752
更新日期:2007-07-15 00:00:00
abstract::In this issue of Blood, Bachanova et al describe how modulation of the inhibitory tumor environment may enhance natural killer (NK) cell clinical activity and produce encouraging results in the treatment of refractory acute myeloid leukemia (AML). NK cells are highly proliferative, early responders of the innate immun...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2014-05-570291
更新日期:2014-06-19 00:00:00
abstract::The effects of the deoxygenation rate on the formation of irreversibly sickled cells (ISCs) were investigated by using metabolically replete sickle cells (SS cells). We found that the formation of ISCs required Ca2+ and that the amount formed depended on the rate of deoxygenation. When less dense SS discocytes were de...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::In this issue of Blood, Khorana and colleagues report a simple and practical model for the prediction of symptomatic venous thrombosis after the initiation of chemotherapy in cancer outpatients. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2008-02-137760
更新日期:2008-05-15 00:00:00
abstract::Two kinds of erythrocytes are released in the blood of irradiated adult hybrid mice grafted with parental fetal liver cells: fetal antigen-bearing erythrocytes (Ft+ cells) and adult-type Ft- erythrocytes. Both are of parental origin, as determined by immune lysis using histocompatibility alloantigens. The latter cells...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::We demonstrated that Flk-1(+) cells derived from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) to suffice as vascular progenitor cells (VPCs). In the present study, we investigated the importance of the stage of ES cell differentiation on effective participat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-06-1877
更新日期:2003-04-01 00:00:00
abstract::Mature megakaryocytes form structures called proplatelets that serve as conduits for platelet packaging and release at vascular sinusoids. Since the megakaryocyte expresses abundant levels of integrin alpha IIb beta3, we have examined a role for fibrinogen in proplatelet development and platelet release alongside that...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-011957
更新日期:2006-09-01 00:00:00
abstract::Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoiet...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-11-011874
更新日期:2006-09-01 00:00:00
abstract::The recent discovery of microRNAs (miRNAs) has revealed a new layer of gene expression regulation, affecting the immune system. Here, we identify their roles in regulating human plasmacytoid dendritic cell (PDC) activation. miRNA profiling showed the significantly differential expression of 19 miRNAs in PDCs after Tol...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-280156
更新日期:2010-12-23 00:00:00
abstract::Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the tr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::Intestinal mucosal mast cells (IMMC) express granule neutral proteases that are regulated by T-cell-derived cytokines, including interleukin-3 (IL-3) and IL-9, and by stem cell factor (SCF). The IMMC-specific chymase, mouse mast cell protease-1 (mMCP-1), is released in substantial quantities into the blood stream duri...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-05-15 00:00:00
abstract::Factor VIII procoagulant protein (VIII:C) purified from commercial factor VIII concentrate contained multiple polypeptides ranging in mol wt from 79,000 to 188,000, all of which were removed from solution by a monoclonal anti-VIII:C antibody specific for a thrombin-sensitive epitope. In a time-course digest of the pur...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract::We confirmed that murine hematopoietic stem cells express the c-kit molecule but not lymphohematopoietic lineage markers. These lineage marker-negative c-kit-positive (Lin- c-kit+) cells were further divided according to the uptake of rhodamine-123 (Rh-123). Approximately 1,000 Lin- c-kit+ rhodamine-123dull cells, whi...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::Plasmin exposure modulates platelet aggregation responses, but a direct effect of plasmin on the platelet fibrinogen receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), has never been conclusively shown in a plasma milieu. To examine this issue, we incubated platelets in platelet-rich plasma with plasmin and measured the ef...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-01-15 00:00:00
abstract::We evaluated the ability of 2 human mAbs directed against TRAILR1 (HGS-ETR1) and TRAILR2 (HGS-ETR2) to kill human myeloma cells. HGS-ETR1 and HGS-ETR2 mAbs killed 15 and 9 human myeloma cell lines (HMCLs; n = 22), respectively. IL-6, the major survival and growth factor for these HMCLs, did not prevent their killing. ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-12-007971
更新日期:2006-08-15 00:00:00
abstract::The administration of greater than or equal to 5 micrograms interleukin-7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::CXC ligand 12 (CXCL12; also known as stromal cell-derived factor 1alpha/SDF-1alpha) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular pept...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-12-3893
更新日期:2003-06-15 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained. We created and analyzed 3 separate iPSC clones from f...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-484444
更新日期:2013-09-19 00:00:00
abstract::Targeted irradiation of the bone marrow with radiolabeled monoclonal antibodies (radioimmunotherapy) represents a novel therapeutic approach with both myeloablative and antileukemic potential. In an open-label, single-center pilot study, 30 pediatric and adolescent patients undergoing hematopoietic cell transplantatio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-06-284349
更新日期:2011-04-28 00:00:00
abstract::An acquired gain-of-function mutation in the Janus kinase 2 (JAK2-V617F) is frequently found in patients with myeloproliferative disorders (MPDs). To test the hypothesis that JAK2-V617F is the disease-initiating mutation, we examined whether all cells of clonal origin carry the JAK2-V617F mutation. Using allele-specif...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2005-11-009605
更新日期:2006-08-15 00:00:00