Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP
| العنوان: | Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP |
|---|---|
| المؤلفون: | Vikram G. Pillai, X. Long Zheng, Jenny K. McDaniel, Jialing Bao, Khalil Bdeir, Douglas B. Cines, Steven H. Seeholzer, Palaniappan Sevugan Chetty, Catherine B. Zander |
| المصدر: | Blood. 128:110-119 |
| بيانات النشر: | American Society of Hematology, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Neutrophils, Proteolysis, Amino Acid Motifs, Immunology, Thrombotic thrombocytopenic purpura, ADAMTS13 Protein, Inflammation, 030204 cardiovascular system & hematology, Cleavage (embryo), Biochemistry, Thrombosis and Hemostasis, Defensins, 03 medical and health sciences, 0302 clinical medicine, Immune system, Von Willebrand factor, hemic and lymphatic diseases, von Willebrand Factor, medicine, Humans, Acquired Thrombotic Thrombocytopenic Purpura, Purpura, Thrombotic Thrombocytopenic, biology, medicine.diagnostic_test, Chemistry, Cell Biology, Hematology, medicine.disease, Molecular biology, ADAMTS13, 030104 developmental biology, cardiovascular system, biology.protein, Female, medicine.symptom, circulatory and respiratory physiology |
| الوصف: | Infection or inflammation may precede and trigger formation of microvascular thrombosis in patients with acquired thrombotic thrombocytopenic purpura (TTP). However, the mechanism underlying this clinical observation is not fully understood. Here, we show that human neutrophil peptides (HNPs) released from activated and degranulated neutrophils inhibit proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 in a concentration-dependent manner. Half-maximal inhibitory concentrations of native HNPs toward ADAMTS13-mediated proteolysis of peptidyl VWF73 and multimeric VWF are 3.5 μM and 45 μM, respectively. Inhibitory activity of HNPs depends on the RRY motif that is shared by the spacer domain of ADAMTS13. Native HNPs bind to VWF73 (KD = 0.72 μM), soluble VWF (KD = 0.58 μM), and ultra-large VWF on endothelial cells. Enzyme-linked immunosorbent assay (ELISA) demonstrates markedly increased plasma HNPs1-3 in most patients with acquired autoimmune TTP at presentation (median, ∼170 ng/mL; range, 58-3570; n = 19) compared with healthy controls (median, ∼23 ng/mL; range, 6-44; n = 18) (P < .0001). Liquid chromatography plus tandem mass spectrometry (LC-MS/MS) reveals statistically significant increases of HNP1, HNP2, and HNP3 in patient samples (all P values |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::272dba7c06e568f4d8e2c4423b34d09f https://doi.org/10.1182/blood-2015-12-688747 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....272dba7c06e568f4d8e2c4423b34d09f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
|---|