The role of immunoglobulin G and fibrinogen in platelet aggregation by Streptococcus sanguis

Previous work has shown that the type strain of Streptococcus sanguis , NCTC 7863, induces aggregation of normal platelets by a complement-dependent mechanism. We investigated the roles of IgG and fibrinogen in the aggregation process. Plasma depleted of IgG by passage through protein A–sepharose failed to support platelet aggregation, as did plasma absorbed at 0°C with whole bacteria. However, absorption of plasma with a non-aggregating strain of S. sanguis , SK96, did not remove aggregating activity for NCTC 7863. Supplementing 0°C-absorbed plasma with purified IgG restored the aggregation supporting activity. A monoclonal antibody to the FcγRII receptor inhibited platelet aggregation by the bacteria, indicating a requirement for bacteria–IgG complexes interacting with the Fc receptor in platelet aggregation. There was a lag time to the onset of platelet aggregation of 7–19 min depending upon the platelet donor, but the length of this lag did not correlate with either total IgG concentration recognizing NCTC 7863 in subjects' plasma, or the concentration any of the four IgG subclasses or with IgG avidity levels.
Fibrinogen was shown to bind rapidly to the bacterial cell surface. Monclonal antibody to GPIIb/IIIa, RGDS peptide, and a specific antagonist for the platelet fibrinogen receptor, GPIIb/IIIa, FK633, inhibited platelet aggregation by NCTC 7863, indicating that platelet aggregation is fibrinogen dependent. These data suggest that platelet aggregation by some strains of S. sanguis requires multiple stimuli/agonists, including IgG–Fc receptor interaction, complement and fibrinogen.     

Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863

We investigated the mechanisms of platelet aggregation by the type strain of Streptococcus sanguis (NCTC 7863). This species is one of the major aetiological agents of infective endocarditis. S. sanguis NCTC 7863 caused aggregation of normal human platelets in vitro following a lag period that varied between donors (7–19 min). Platelet aggregation was dependent on one or more plasma consistuents and all the necessary factors gradually became bound to the bacterial surface during the lag period. The length of the lag period was determined by the plasma of the donor and not by a feature of their platelets. Platelet aggregation by S. sanguis NCTC 7863 could be inhibited by heating plasma at 56°C, by treating plasma with cobra venom factor, or by incubating with soluble Complement Receptor 1, all of which inhibit or deplete complement. Complement activation required Mg²⁺, but not Ca²⁺ ions and the the cleavage fragment, Ba, of factor B was produced, indicating that the alternative pathway was operative. Zymosan- and S. sanguis -induced aggregation showed similarities, including the same variability in lag times among donors, and absorption of plasma with zymosan prevented the plasma from supporting platelet aggregation by S. sanguis . C3, C9 and vitronectin were found to bind to S. sanguis NCTC 7863, but the latter two were present at very low levels on a non-aggregating strain of S. sanguis , SK96. The rate of assembly of the C5b–9 complex on the NCTC 7863 bacterial surface correlated with the lag time. These data suggest a role for the complement pathway in platelet aggregation by the type strain of S. sanguis .     

阻塞性睡眠呼吸暂停低通气综合征相关心脏损伤的影像研究进展

阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea syndrome,OSAS)是一种常见的呼吸系统疾病,表现为睡眠过程中反复低通气及呼吸暂停。OSAS通过缺氧复氧性损伤、交感神经系统激活、系统性炎症因子介导等多种方式损伤心血管系统,引起血管内皮功能紊乱、心脏增大、心肌肥厚及心功能降低等病理生理改变。超声心动图及心脏磁共振(cardiac magnetic resonance,CMR)是心脏结构及功能评估的常用手段,本文就OSAS致心脏损伤的影像研究进展做一综述。     

A case of infective endocarditis in a farmer caused by Streptococcus equinus

The following is a case report of a farmer with documented aorticvalve disease who developed bacterial endocarditis secondaryto Streptococcus equinus. This is a rare pathogen in man andits acquisition in this case may be related to the subject'soccupation.     

Destructive endocarditis caused by Streptococcus sanguis on normal valves after gastroduodenoscopy

In recent years, epidemiological and clinical patterns in infective endocarditis are changed: mean age of patients, sex, underlying cardiac diseases, source of bacteremia, availability of better diagnostic methods--specially two-dimensional and doppler echocardiography--and surgical options. The Authors report a paradigmatic case of a young man without cardiac disease, who developed a destructive endocarditis complicated by refractory congestive heart failure; the cause was an organism of low pathogenicity, Streptococcus sanguis, that entered the bloodstream after gastroduodenoscopy.     

Mechanisms of platelet aggregation

Platelet aggregation is initiated by receptor activation coupled to intracellular signaling leading to activation of integrin alphaIIbbeta3. Recent advances in the study of platelet receptors for collagen, von Willebrand factor, thrombin, and adenosine diphosphate are providing new insights into the mechanisms of platelet aggregation.     

A case of infective endocarditis due to Streptococcus agalactiae

A 60 year-old woman, who was pointed out as having hyperglycemia, was admitted to our hospital, with a two-week history of fever. Blood sugar on admission was 424 mg/dl and blood cultures yielded Streptococcus agalactiae. Systolic and diastolic heart murmurs were heard. Echocardiography showed aortic regurgitation and vegetation on the aortic valve. Penicillin-G (4 million units every 4 hr) iv and streptomycin (1 g every 12 hr) im were started. Chemotherapy was continued for 48 days. After chemotherapy, aortic valve replacement was done. We reported a very rare infective endocarditis case due to Streptococcus agalactiae.     

FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation

The bacterium Streptococcus agalactiae is an etiologic agent in the pathogenesis of endocarditis in humans. FbsA, a fibrinogen-binding protein produced by this pathogen, is considered an important virulence factor. In the present study we provide evidence that S agalactiae clinical isolates bearing FbsA attach to fibrinogen and elicit a fibrinogen-dependent aggregation of platelets. Mutants of S agalactiae lacking the fbsA gene lost the ability to attach to fibrinogen and to aggregate platelets. Plasmid-mediated expression of fbsA restored the capability for fibrinogen binding and platelet aggregation in S agalactiae fbsA mutants, and allowed Lactococcus lactis to interact with fibrinogen and to aggregate human platelets. Moreover, a monoclonal anti-FbsA antibody inhibited bacterial adherence to fibrinogen and S agalactiae-induced platelet aggregation. Platelet aggregation was inhibited by aspirin, prostaglandin E(1,) the peptide RGDS, and the antibody abciximab, demonstrating the specificity of platelet aggregation by S agalactiae and indicating an involvement of integrin glycoprotein IIb/IIIa in the induction of platelet aggregation. Aggregation was also dependent on anti-FbsA IgG and could be inhibited by an antibody against the platelet FcgammaRIIA receptor. These findings indicate that FbsA is a crucial factor in S agalactiae-induced platelet aggregation and may therefore play an important role in S agalactiae-induced endocarditis.     

Mean platelet volume and mean platelet volume/platelet count ratio in infective endocarditis

Abstract

Infective endocarditis (IE), an infection of the endocardial surface, frequently leads to life-threatening complications, such as thromboembolism due to platelet activation. We investigated the mean platelet volume (MPV) in Korean patients with IE and the serial changes thereof, in comparison with other laboratory parameters. We analyzed 248?MPV results from 22 patients diagnosed with IE in our hospital between January 2011 and April 2012. MPV was measured with an Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown, NY) using EDTA-containing tubes. The mean MPV differed significantly between the patient and control groups, 8.74 vs. 7.96?fl, respectively. In addition, the platelet count and MPV/platelet count ratio were significantly decreased in the patient group. The total platelet mass and platelet size in IE might be increased. Further studies should examine more patients to verify the changes in the MPV and MPV/platelet count ratio in IE and assess in greater detail the relationship between MPV and thrombotic complications caused by platelet activation.     

Streptococcus agalactiae infective endocarditis with large vegetation in a patient with underlying protein S deficiency

We present a case of a patient with underlying protein S deficiency who suffered from infective endocarditis with a large anterior mitral leaflet (AML) mass of approximately 4.5 cm in length. Intraoperative transesophageal echocardiography (TEE) revealed the mass at the AML base and a rupture of the posterior mitral leaflet chordae tendinae. The vegetation’s large size may have been caused by one or more of three factors: location, underlying disease, and the microorganism causing infection. Patients with protein S deficiency are prone to thromboembolic events during cardiac surgery. Infective endocarditis caused by Streptococcus agalactiae usually has a poor prognosis, and, thus, early surgery is recommended.     

Mechanisms of abnormal platelet aggregation in systemic lupus erythematosus

Platelet aggregation was measured in 14 patients with systemic lupus erythematosus (SLE) and 13 normal controls. Ten SLE patients (group I) showed decreased responsiveness to collagen, while aggregation was normal in 4 (group II). Group I patients also responded poorly to epinephrine. Platelets from SLE patients did not differ from controls in the production of malondialdehyde in response to N-ethylmaleimide, suggesting intact prostaglandin synthetic pathways. However, a significant decrease (P < 0.005) in platelet levels of the dense granule constituent, serotonin, was noted in group I SLE patients. Treatment of SLE platelet-rich plasma with deoxyribonuclease (DNase) resulted in enhancement of collagen-induced aggregation in 4 group I SLE patients, but not in 1 group II or 8 normal individuals. These results suggest that defective aggregation in SLE platelets may be partially related to a storage pool deficiency state. However, the ability to restore aggregation to collagen by digestion of platelet-rich plasma with DNase indicates that the defect is reversible and that it is perhaps mediated by plasma or platelet-associated DNA.     

感染性心内膜炎链球菌耐药基因检测与分析

目的通过分析感染性心内膜炎链球菌的耐药基因,以便有效控制链球菌耐药性的进一步发展,从而为感染性心内膜炎的治疗提供依据。方法从感染性心内膜炎患者血培养标本中分离链球菌,提取DNA,采用PCR方法检测耐药基因,并作测序分析。结果 PCR检测链球菌9种耐药基因,其中gyrA、parC、tetM基因扩增均阳性,且同源性较高。所有菌株的tetM基因同源性均为100%。有3株发生突变,突变位点分别为81位、87位和79位,且突变株均对氟喹诺酮类抗菌药物耐药。链球菌耐药基因编码氨基酸序列比对图显示,gyrA第81位由丝氨酸(Ser)突变为精氨酸(Arg),parC第87位由精氨酸(Arg)变异为亮氨酸(Leu),parC第79位由丝氨酸(Ser)突变为苯丙氨酸(Phe),因而可能导致耐药性的产生。结论分离自感染性心内膜炎患者的链球菌含有gyrA、parC、tetM基因,这3种基因可能与链球菌的耐药性有关。     

Reactive arthritis and subacute infective endocarditis caused by Streptococcus gordonii infection: A case report

Streptococcus gordonii (S. gordonii) belongs to the alpha-hemolytic Streptococcus group. It is a symbiotic bacterium found in the human oral mucosa which is present in large quantities on the surface of the teeth. It is generally considered nonpathogenic or weakly pathogenic and is known to cause subacute endocarditis; however, there are few reports of reactive arthritis (ReA) caused by S. gordonii. Herein, we report a case of ReA complicated by subacute infective endocarditis caused by S. gordonii and explore the possible pathogenic mechanism of ReA caused by S. gordonii.