Association of natural anti-platelet factor 4/heparin antibodies with periodontal disease
Andreas GreinacherBirte HoltfreterKrystin KrauelDaniela GätkeClaudia E. WeberTill IttermannSven HammerschmidtThomas Kocher
105
Citation
42
Reference
10
Related Paper
Citation Trend
Keywords:
Aggregatibacter actinomycetemcomitans
PF4 has a half-life in plasma of less than 3 minutes, and its rapid clearance appears to be a function of binding to the vascular endothelium. Once bound to the endothelium, PF4 can be released by heparin in a time-dependent manner; recovery is greater the sooner heparin is administered following PF4 infusion. This heparin-induced release of PF4 can be abolished if the heparin is first complexed with hexadimethrine bromide. Likewise, this heparin-induced release of PF4 is dependent upon the type of heparin used; low molecular weight heparin fractions and fragments do not cause the PF4 rebound seen with intact heparin. Thus, it would appear that low molecular weight forms of heparin are advantageous in that their in vivo administration would not be mediated by such platelet modulators as PF4.
Cite
Citations (29)
Heparin-Induced Thrombocytopenia
Cite
Citations (46)
Review Articles| June 30 2006 Heparin-Induced Thrombocytopenia: Frequency and Pathogenesis Subject Area: Cardiovascular System , Hematology , Pathology and Cell Biology A. Greinacher A. Greinacher Search for other works by this author on: This Site PubMed Google Scholar Pathophysiology of Haemostasis and Thrombosis (2006) 35 (1-2): 37–45. https://doi.org/10.1159/000093542 Article history Published Online: June 30 2006 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation A. Greinacher; Heparin-Induced Thrombocytopenia: Frequency and Pathogenesis. Pathophysiology of Haemostasis and Thrombosis 1 May 2006; 35 (1-2): 37–45. https://doi.org/10.1159/000093542 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPathophysiology of Haemostasis and Thrombosis Search Advanced Search This content is only available via PDF. 2006Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Article PDF first page preview Close Modal You do not currently have access to this content.
Heparin-Induced Thrombocytopenia
Pathogenesis
Immune complex
Cite
Citations (32)
Affinities
Cite
Citations (17)
Heparin-platelet factor 4 (H-PF4) complexes are the target for heparin-dependent antibodies present in most of heparin-induced thrombocytopenias (HIT). The highest reactivity is obtained with 27 IU of heparin per mg of PF4. Low molecular weight heparin (LMWH) and pentosane polysulphate can also form these complexes. Antibodies to H-PF4, may be of the IgG, IgA or IgM isotypes. In some HIT, IgGs are absent and only IgMs and/or IgAs are observed. These antibodies may also develop in heparin (15%) or LMWH (8%) treated patients in the absence of thrombocytopenia. IgGs rarely develop in these cases. Presence of antibodies to H-PF4 is therefore a risk factor for developing HIT. Development of pathology requires additional factors such as: PF4 and heparin at an optimised ratio allowing formation of macromolecular complexes; presence of activated platelets exposing increased Fc gamma RII-A and heparin receptors; His. 131 phenotype of Fc gamma RII-A; pre-thrombotic and/or inflammatory clinical manifestations. Assay of antibodies to H-PF4 improves HIT diagnosis and could be predictive for monitoring heparin-therapies.
Heparin-Induced Thrombocytopenia
Cite
Citations (4)
Periodontitis is an inflammatory disease caused by Porphyromonas gingivalis (P. gingivalis) in the oral cavity. This periodontal disease causes damage to the periodontal ligament and alveolar bone and can cause tooth loss, but there is no definite treatment yet. In this study, we investigated the possibility of using no-ozone cold plasma to safely treat periodontitis in the oral cavity. First, human gingival fibroblasts (HGFs) were treated with P. gingivalis-derived lipopolysaccharide (PG-LPS) to induce an inflammatory response, and then the anti-inflammatory effect of NCP was examined, and a study was conducted to identify the mechanism of action. Additionally, the anti-inflammatory effect of NCP was verified in rats that developed an inflammatory response similar to periodontitis. When NCP was applied to PG-LPS-treated HGFs, the activities of inflammatory proteins and cytokines were effectively inhibited. It was confirmed that the process of denaturing the medium by charged particles of NCP is essential for the anti-inflammatory effect of NCP. Also, it was confirmed that repeated treatment of periodontitis rats with NCP effectively reduced the inflammatory cells and osteoclast activity. As a result, this study suggests that NCP can be directly helpful in the treatment of periodontitis in the future.
Anti-inflammatory
Periodontal fiber
Cite
Citations (1)
Periodontitis is a disease that leads to bone destruction and represents the main cause of tooth loss in adults. The development of aggressive periodontitis has been associated with increased inflammatory response that is induced by the presence of a subgingival biofilm containing Aggregatibacter actinomycetemcomitans. The flavonoid quercetin (1) is widespread in vegetables and fruits and exhibits many biological properties for possible medical and clinical applications such as its anti-inflamatory and antioxidant effects. Thus, in the present study, the properties of 1 have been evaluated in bone loss and inflammation using a mouse periodontitis model induced by A. actinomycetemcomitans infection. Subcutaneous treatment with 1 reduced A. actinomycetemcomitans-induced bone loss and IL-1β, TNF-α, IL-17, RANKL, and ICAM-1 production in the gingival tissue without affecting bacterial counts. These results demonstrated that quercetin exhibits protective effects in A. actinomycetemcomitans-induced periodontitis in mice by modulating cytokine and ICAM-1 production.
Aggregatibacter actinomycetemcomitans
Tooth loss
Cite
Citations (71)
Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are major periodontal pathogens that cause several types of periodontal disease. Our previous study suggested that P. gingivalis gingipains secreted in the subgingival environment are related to the detachment of A.actinomycetemcomitans biofilms. However, it remains unclear whether arginine-specific cysteine proteinase (Rgp) and lysine-specific proteinase (Kgp) play different roles in the detachment of A. actinomycetemcomitans biofilm. The aim of this study was to investigate possible disruptive roles of Kgp and Rgp in the aggregation and attachment of A. actinomycetemcomitans. While P. gingivalis ATCC33277 culture supernatant has an ability to decrease autoaggregation and coaggregation of A. actinomycetemcomitans cells, neither the boiled culture supernatant of ATCC33277 nor the culture supernatant of KDP136 showed this ability. The addition of KYT-1 and KYT-36, specific inhibitors of Rgp and Kgp, respectively, showed no influence on the ability of P. gingivalis culture supernatant. The result of gelatin zymography suggested that other proteases processed by gingipains mediated the decrease of A. actinomycetemcomitans aggregations. We also examined the biofilm-destructive effect of gingipains by assessing the detachment of A. actinomycetemcomitans from polystyrene surfaces. Scanning electron microscope analysis indicated that A. actinomycetemcomitans cells were detached by P. gingivalis Kgp. The quantity of A. actinomycetemcomitans in biofilm was decreased in co-culture with P. gingivalis. However, this was not found after the addition of KYT-36. These findings suggest that Kgp is a critical component for the detachment and decrease of A. actinomycetemcomitans biofilms.
Aggregatibacter actinomycetemcomitans
Cite
Citations (24)
Abstract Background The facultative bacterium Aggregatibacter actinomycetemcomitans (Aa) is strongly associated with periodontitis and is occasionally found in periodontally healthy subjects. We aimed to determine the prevalence of salivary Aa among patients with either periodontitis Grade B (periodontitis‐B) or Grade C (periodontitis‐C), periodontally healthy controls (HCs), and to determine if systemic antibodies against Aa or its virulence factor leukotoxin A (LtxA) may serve as biomarkers that reveal the oral presence of the bacterium and discriminate subjects with periodontitis‐C, periodontitis‐B, or no periodontitis from each other. Methods Serum and unstimulated saliva samples were collected from patients with periodontitis‐C (n = 27), patients with periodontitis‐B (n = 34), and HCs (n = 28). Serum level of immunoglobulin G antibodies to fragmented whole Aa and to LtxA were quantified using a bead‐based assay. Aa was identified in saliva using quantitative polymerase chain reaction (qPCR). All analyses were adjusted for age, sex, and current smoking status. Results Aa was present in saliva from 11% of HCs, in 32% of patients with periodontitis‐B ( P = 0.04 versus HCs), and in 37% of patients with periodontitis‐C ( P = 0.02 versus HCs). Serum antibodies to fragments of Aa associated significantly with periodontitis‐C ( P = 0.03), while serum anti‐LtxA antibodies associated with both periodontitis‐B and periodontitis‐C ( P = 0.002 and P = 9×10 −4 , respectively). Moreover, a significant association between serum anti‐LtxA antibodies and Aa count in saliva was observed ( P = 0.001). On the basis of serum anti‐LtxA antibody levels, patients with periodontitis could be discriminated from HCs (AUC = 0.74 in ROC curve‐analysis, P = 0.0003), and carriers of Aa could be discriminated from non‐carriers (AUC = 0.78, P <0.0001). Conclusions Aa is highly prevalent in saliva of patients with periodontitis‐B or periodontitis‐C. Systemic immunoglobulin G antibodies against LtxA distinguish patients with periodontitis, regardless of grade, from HCs, while their quantity reflects the concurrent bacterial burden in the oral cavity.
Aggregatibacter actinomycetemcomitans
Aggressive periodontitis
Cite
Citations (5)
Heparin-induced thrombocytopenia (HIT) is mediated by antibody against complexes of platelet factor-4 (PF4) and heparin. Although it has been assumed that these complexes bind to platelets and provide a target for the antibody, this has never been demonstrated. Furthermore, there is evidence suggesting that heparin-PF4 complexes do not bind to platelets. We have analyzed the effect of each ligand on the platelet binding of the other. We particularly focused on the result when heparin and PF4 are in equimolar concentration because we had previously shown that this was the condition under which HIT-IgG increased on the platelet surface. We found that when the molar concentration of PF4 approximates or exceeds that of heparin, the ligands bind simultaneously to the cells and HIT-IgG binds also. However, when heparin is in molar excess, both PF4 binding and HIT-IgG binding are diminished. Our data are consistent with the hypothesis that heparin-PF4 complexes bind via their heparin component to heparin binding sites on the platelet membrane rather than by their PF4 component to PF4 sites. The conditions promoting the binding of the complexes also lead to binding of HIT-IgG. Am. J. Hematol. 58:24–30, 1998. © 1998 Wiley-Liss, Inc.
Heparin-Induced Thrombocytopenia
Cite
Citations (52)