GP IIb/IIIa-ICAM-1 Mediated Platelet-Endothelial Adhesion Exacerbates Pulmonary Hypertension
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PROVIDER: PRJNA1194190 | ENA |
REPOSITORIES: ENA
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Project description:Pulmonary hypertension (PH) patients typically present with a diminished platelet count, but the role of platelets in the development and progression of PH remains unclear.Transcriptomic analysis revealed that platelets from PH patients exhibited an upregulation of genes associated with cellular adhesion, platelet activation, and adhesion. Notably, the hub genes, glycoprotein IIb/IIIa (GP IIb/IIIa), were implicated in mediating platelet-endothelium adhesion through their interaction with intercellular adhesion molecule-1 (ICAM-1) on pulmonary artery endothelial cells, triggering platelet activation and the subsequent release of platelet-derived growth factor BB (PDGF-BB).
2024-12-09 | GSE283520 | GEO
Project description:Candida albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted. Previous studies have identified an essential role of platelets in infection and immunity, especially when they are activated. However, it is still unclear whether platelets can be activated by C. albicans, and even less is known about the role of platelets in C. albicans infection. Herein, we showed that C. albicans induced platelet activation in vitro. C. albicans elevated the levels of AKT Ser473 phosphorylation, and inhibition of the PI3K-AKT signaling pathway reversed C. albicans-induced platelet activation. Surprisingly, C. albicans-induced platelet activation occurred in an integrin glycoprotein (GP) IIb/IIIa-dependent manner but was independent of the pattern recognition receptors toll-like receptor (TLR) 2 and TLR4. Interestingly, platelets enhanced the phagocytosis of human monocytes challenged with C. albicans and upregulated the expression of inflammatory cytokines, which were dependent on platelet activation mediated by GP IIb/IIIa. The present work provides new insights into the role of activated platelets in the defense against C. albicans, highlighting the importance of GP IIb/IIIa in the recognition of C. albicans.
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Project description:Gene expression profile in laser-dissected islets of Langerhans in the inducible RIP-LCMV-GP mouse model for type 1 diabetes (T1D) RIP-LCMV-GP mice express the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) in the beta-cells (rat insulin promotor, RIP); T1D develops 10-14 after LCMV-infection
2023-10-01 | GSE229287 | GEO
Project description:Site-specific glycosylation analysis by nLC-MS/MS of recombinant human Fcγ receptors IIA (H&R167 isoforms), IIB and murine Fcγ receptor IIB.
2024-08-10 | PXD049429 | Pride
Project description:BackgroundWe previously described a mouse model in which platelet immunization between selected strains leads to production of alloantibodies and severe autoimmune thrombocytopenia and mimics the human condition posttransfusion purpura (PTP). This report describes studies defining epitopes recognized by these alloantibodies.Study designHybridomas were produced from spleen cells of immunized mice. Glycoprotein (GP) targets of resulting monoclonal antibodies were characterized by immunoprecipitation using platelets from the immunizing strains. Antigens defined by single amino acid (AA) polymorphisms recognized by monoclonal antibodies were identified by mutagenizing target glycoproteins expressed in Chinese hamster ovary cells and observing the effects on antibody binding.ResultsThree monoclonal antibodies (417.1, 417.3, 425.1) were produced that recognized GPIIb on immunizing platelets. Monoclonal antibodies 417.1 and 417.3 both required G111 and 425.1 required V37, located on the beta propeller domain of GPIIb, for binding to platelets from the immunizing strains C57 and PWK, respectively. Injection of 417.3 and 425.1 into mice caused platelet destruction only in mice with GPIIb containing the targeted AAs.ConclusionsFindings made provide evidence that alloantibodies produced by mice experiencing thrombocytopenia in a mouse model of PTP are specific for single AA polymorphisms that differ in GPIIb/IIIa integrin of the immunizing and immunized strains and therefore closely resemble the potent alloantibodies found in patients with PTP. The observations show that naturally occurring single AA differences in GPIIb/IIIa integrin of various mouse strains are highly immunogenic in the mouse strains studied and readily induce antibodies comparable to human platelet antigen-specific antibodies found in transfused and pregnant humans.
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Project description:Binding sites on glycoprotein (GP) IIb/IIIa exposed by 0.5 unit/ml alpha-thrombin are insensitive to prostaglandin I2 (PGI2), in contrast with sites exposed by ADP or platelet-activating factor. Here we show that the thrombin receptor agonist peptide (TRAP) (SFLLRN; 15 microM) opens almost the same number of GPIIb/IIIa molecules as 0.5 unit/ml alpha-thrombin (64840 +/- 8920 compared with 81050 +/- 6030 molecules of fibronectin bound/platelet), but these sites rapidly close on addition of PGI2. To investigate whether alpha-thrombin and TRAP initiate different signalling pathways, we measured phospholipase C (PLC)-mediated control of GPIIb/IIIa and its sensitivity to cyclic AMP. Optimal concentrations of alpha-thrombin and TRAP activated PLC maximally, but TRAP induced only about 50% protein kinase C PKC) activation after 10 min stimulation compared with alpha-thrombin. These concentrations also suppressed PGI2-induced cyclic AMP accumulation, with alpha-thrombin inducing complete inhibition and TRAP about 10% less. Direct activation of PKC by phorbol 12-myristate 13-acetate confirmed earlier observations that PGI2-induced cyclic AMP accumulation is partly inhibited via PKC. Applying different concentration of alpha-thrombin, TRAP or a combination of alpha-thrombin and the thrombin receptor inhibitory peptide (TRIP) (Mpr-F-Cha-Cha-RKPNDK-NH2; 800 microM) (Mpr, 3-mercaptopropionic acid; Cha, cyclohexylalanine), we show that the different means of stimulating the thrombin receptor all suppressed PGI2-induced cyclic AMP accumulation via (i) activation of PKC and (ii) activation of the heterotrimeric G-protein, Gi. We conclude that complete inhibition of cyclic AMP accumulation requires activation of both PKC and Gi, as observed with 0.5 unit/ml alpha-thrombin. Although TRAP almost fully exposes GPIIb/IIIa, its activation of PKC is incomplete, enabling PGI2 to raise cyclic AMP concentration from 1.4 +/- 0.7 to 4.1 +/- 1.3 nmol/10(11) platelets (P < 0.005) which is sufficient to close exposed GPIIb/IIIa molecules.
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Project description:The envelope glycoprotein GP of the ebolaviruses is essential for host cell attachment and entry. It is also the primary target of the protective and neutralizing antibody response in both natural infection and vaccination. GP is heavily glycosylated with up to 17 predicted N-linked sites, numerous O-linked glycans in its disordered mucin-like domain (MLD), and three predicted C-linked mannosylation sites. Glycosylation of GP is important for host cell attachment to cell-surface lectins, as well as GP stability and fusion activity. Moreover, it has been shown to shield GP from neutralizing activity of serum antibodies. Here, we use mass spectrometry-based glycoproteomics to profile the site-specific glycosylation patterns of ebolavirus GP, including N-, O-, and C-linked glycans.
2022-08-02 | PXD031459 | Pride
Project description:Signal intensities of BC-GP array for 105 speimens The Verigene Gram-Positive Blood Culture (BC-GP) nucleic acid assay is an automated microarray-based test, which can detect 12 Gram-positive bacterial genes and 3 resistance determinants using blood culture broths. We investigated signal intensities of microarray spots, and reclassified undetermined results where the automated system failed and various errors were called in blood culture specimens and spiked samples.
2014-05-30 | GSE57245 | GEO
Project description:The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1-/-) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favors myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSCs quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1-/- mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche.
2018-06-21 | GSE114836 | GEO
Project description:The project contains raw and result files of a proteomics analysis of two patients with type 1 Glanzmann thrombasthenia (Patient1 and 2) caused by homozygous ITGA2b delG mutations and from family (heterozygous: Father1, Mother1, Sister1, healthy: Sister2) and unrelated controls. A label-free analysis has been conducted in duplicates using Progenesis (NonLinear Dynamics) demonstrating that less than 5% of glycoprotein IIb and 5-7% fibrinogen is expressed compared to healthy controls. Heterozygous familiy members from one of the controls expressed 50-60% of GPIIb sufficient for normal GPIIb/IIIa-dependant platelet function. In a subsequent targeted LC-MS/MS analysis we quantified 14 protein identified as potentially regulated in preliminary iTRAQ experiments. We observed diminished expession of factor XIIIB chain (P05160), plasminogen (P00747) and carboxypeptidase 2B (Q96IY4) in thrombasthenic platelets as well as a 2.5-fold increased expression of FcgRIIA (P12318/P31995) and laminin alpha4 (Q16363).
2019-01-14 | PXD003912 | Pride