Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: C-reactive protein (CRP) exerts prothrombotic effects through dissociating from pentameric CRP (pCRP) into modified or monomeric CRP (mCRP). However, although the high prevalence of venous thromboembolism (VTE) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been identified, it remains unclear whether the high levels of circulating pCRP potentially contribute to this hypercoagulable state in AAV. ANCA can induce the generation of neutrophil extracellular traps (NETs). In this study, the NETs-dependent generation of mCRP from pCRP and the influences of mCRP on the activation of coagulation system and inflammatory response in AAV were investigated.
Results: NETs were induced after TNF-α primed neutrophils were incubated with ANCA-containing IgG. After ANCA-induced netting neutrophils were incubated statically with platelet-rich plasma (PRP) containing mCRP (60 μg/mL), the proportion of platelets expressing CD62p increased significantly, while no increased CD62p expression of platelets was observed after static incubation with PRP containing pCRP (60 μg/mL). Under flow conditions, perfusing immobilized ANCA-induced netting neutrophils with pCRP-containing PRP caused platelets activation and mCRP deposition. The newly generated mCRP induced platelets activation on ANCA-induced netting neutrophils, enhanced D-dimer formation, and enhanced high mobility group box 1 secretion by platelets.
Conclusions: Under flow conditions, ANCA-induced netting neutrophils can activate platelets and then prompt the formation of mCRP on activated platelets. Then the newly generated mCRP can further enhance the activation of platelets, the process of thrombogenesis, and the inflammatory response. So the high level of circulating pCRP is not only a sensitive marker for judging the disease activity, but also a participant in the pathophysiology of AAV.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357196 | PMC |
http://dx.doi.org/10.1186/s12865-015-0077-0 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!