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1.
Hsiao-Hsuan Kuo Ran Fan Nina Dvorina Andres Chiesa-Vottero William M. Baldwin III 《Journal of the American Society of Nephrology : JASN》2015,26(4):855-863
Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. 相似文献
2.
Ana Lopez Alonso 《Platelets》2015,26(4):317-323
AbstractWhile the interactions between Gram-positive bacteria and platelets have been well characterized, there is a paucity of data on the interaction between other pathogens and platelets. However, thrombocytopenia is a common feature with many infections especially viral hemorrhagic fever. The little available data on these interactions indicate a similarity with bacteria-platelet interactions with receptors such as FcγRIIa and Toll-Like Receptors (TLR) playing key roles with many pathogens. This review summarizes the known interactions between platelets and pathogens such as viruses, fungi and parasites. 相似文献
3.
对13例体外循环病人进行了观察,发现体外循环后TXB2/6-keto-PGF1α显著增高,表明体外循环使血小板受损,而血小板受损是体外循环后失血的主要原因之一。 相似文献
4.
K. KARNICKI† R. D. MCBANE II † R. S. MILLER† R. J. Leadley JR ¶ J. MORSER W. G. OWEN†‡ J. H. CHESEBRO§ 《Journal of thrombosis and haemostasis》2004,2(12):2162-2169
BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective. 相似文献
5.
Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS 总被引:2,自引:0,他引:2
I. FUCHS† M. FROSSARD† A. SPIEL E. RIEDMÜLLER† A. N. LAGGNER† B. JILMA 《Journal of thrombosis and haemostasis》2006,4(12):2547-2552
BACKGROUND: Platelet hyperfunction contributes to acute coronary syndromes (ACS). Thus, we hypothesized that platelet function under high shear stress predicts recurrent ACS during long-term follow-up of ACS patients. PATIENTS AND METHODS: Consecutive ACS patients (n = 208) were prospectively followed-up for an average of 28 months. Platelet function was measured with the platelet function analyzer (PFA-100; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. RESULTS: Of the conventional risk factors, only the prevalence of diabetes was higher in ACS patients with re-events. However, use of clopidogrel and use of beta blockers were also slightly lower in patients with re-events (P < 0.05). The unadjusted risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI): 1.4-7.4; P = 0.005] in those patients with the shortest CADP-CT values (lowest quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P = 0.02) in ACS patients with CEPI-CT < 300 s as compared with CEPI-CT >or = 300 s. Inclusion of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P = 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8-9.8; P = 0.11). CONCLUSION: Shortened CT values reflect biologically relevant platelet hyperfunction in patients with ACS because they predict recurrent ACS. 相似文献
6.
B. PATEL M. SHARIFI A. D. MILWARD N. G. OBERPRIELER J. M. GIBBINS† S. PARKIN K. M. NASEEM 《Journal of thrombosis and haemostasis》2006,4(11):2423-2432
BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity in endothelial cells is regulated by post-translational phosphorylation of critical serine, threonine and tyrosine residues in response to a variety of stimuli. However, the post-translational regulation of eNOS in platelets is poorly defined. OBJECTIVES: We investigated the role of tyrosine phosphorylation in the regulation of platelet eNOS activity. METHODS: Tyrosine phosphorylation of eNOS and interaction with the tyrosine phosphatase SHP-1 were investigated by coimmunoprecipitation and immunoblotting. An in vitro immunoassay was used to determine eNOS activity together with the contribution of protein tyrosine phosphorylation. RESULTS: We found platelet eNOS was tyrosine phosphorylated under basal conditions. Thrombin induced a dose- and time-dependent increase in eNOS activity without altering overall level of tyrosine phosphorylation, although we did observe evidence of minor tyrosine dephosphorylation. In vitro tyrosine dephosphorylation of platelet eNOS using a recombinant protein tyrosine phosphatase enhanced thrombin-induced activity compared to thrombin alone, but had no effect on endothelial eNOS activity either at basal or after stimulation with bradykinin. Having shown that dephosphorylation could modulate platelet eNOS activity we examined the role of potential protein phosphatases important for platelet eNOS activity. We found SHP-1 protein tyrosine phosphatase, co-associated with platelet eNOS in resting platelets, but does not associate with eNOS in endothelial cells. Stimulation of platelets with thrombin increased SHP-1 association with eNOS, while inhibition of SHP-1 abolished the ability of thrombin to induce elevated eNOS activity. CONCLUSIONS: Our data suggest a novel role for tyrosine dephosphorylation in platelet eNOS activation, which may be mediated by SHP-1. 相似文献
7.
8.
Thrombosis triggered by severe arterial lesions is inhibited by oral administration of a glycoprotein IIb/IIIa antagonist 总被引:2,自引:0,他引:2
J. J. BADIMON B. MEYER L. P. FEIGEN D. A. BARON J. H. CHESEBRO V. FUSTER & L. BADIMON 《European journal of clinical investigation》1997,27(7):568-574
Platelet aggregation and thrombosis play an important role in the onset of acute coronary events. Regardless of the stimulus for activation, platelet thrombus formation is ultimately regulated through the IIb/IIIa receptor complex. The effects of oral administration of xemilofiban, a non-peptide mimetic of the RGDF sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated in a canine model. Xemilofiban significantly reduced platelet deposition on severely damaged arterial wall. Platelet deposition was reduced at both low (13 ± 1 from 56 ± 18 × 106 platelets cm−2 ; P < 0.05) and high (23 ± 2 from 111 ± 21 × 106 platelets cm−2 ; P < 0.01) shear rates. Platelet deposition was reduced to a monolayer as seen by electron microscopy (platelet–vessel wall interaction). Therefore, the availability of an orally active IIb/IIIa antagonist for chronic use may have significant value in preventing thrombus formation in those clinical situations associated with severe arterial injury, such as atherosclerotic plaque disruption. 相似文献
9.
Summary. Platelet membranes provide procoagulant surfaces for the assembly and expression of the factor X-activating complex and promote the proteolytic activation and assembly of the prothrombinase complex resulting in normal hemostasis. Recent studies from our laboratory and others indicate that platelets possess specific, high-affinity, saturable, receptors for factors XI, XIa, IX, IXa, X, VIII, VIIIa, V, Va and Xa, prothrombin, and thrombin. Studies described in this review support the hypothesis that the factor X-activating complex on the platelet surface consists of three receptors (for the enzyme, factor IXa; the substrate, factor X; and the cofactor, factor VIIIa), the colocalization of which results in a 24 million-fold acceleration of the rate of factor X activation. Whether the procoagulant surface of platelets is defined exclusively by procoagulant phospholipids, or whether specific protein receptors exist for the coagulant factors and proteases, is currently unresolved. The interaction between coagulation proteins and platelets is critical to the maintenance of normal hemostasis and is pathogenetically important in human disease. 相似文献
10.