Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice
<p> <b>Background</b> von Willebrand factor (vWF) plays an important role in platelet activation. CD40-CD40 ligand (CD40L) induced vWF release has been described in large vessels and cultured endothelium, but its role in the microcirculation is not known. Here, we studied whether C...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
[2020]
|
| In: |
Thrombosis and haemostasis
Year: 2020, Jahrgang: 120, Heft: 3, Pages: 466-476 |
| ISSN: | 2567-689X |
| DOI: | 10.1055/s-0040-1702228 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1055/s-0040-1702228 Verlag, lizenzpflichtig, Volltext: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0040-1702228 
|
| Verfasserangaben: | Sibgha Tahir, Andreas H. Wagner, Steffen Dietzel, Hanna Mannell, Joachim Pircher, Ludwig T. Weckbach, Markus Hecker, Ulrich Pohl |
MARC
| LEADER | 00000caa a22000002c 4500 | ||
|---|---|---|---|
| 001 | 1695006003 | ||
| 003 | DE-627 | ||
| 005 | 20231026105316.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200420s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1055/s-0040-1702228 |2 doi | |
| 035 | |a (DE-627)1695006003 | ||
| 035 | |a (DE-599)KXP1695006003 | ||
| 035 | |a (OCoLC)1341315618 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Tahir, Sibgha |e VerfasserIn |0 (DE-588)1151463108 |0 (DE-627)1011808676 |0 (DE-576)497768321 |4 aut | |
| 245 | 1 | 0 | |a Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice |c Sibgha Tahir, Andreas H. Wagner, Steffen Dietzel, Hanna Mannell, Joachim Pircher, Ludwig T. Weckbach, Markus Hecker, Ulrich Pohl |
| 264 | 1 | |c [2020] | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 20.04.2020 | ||
| 520 | |a <p> <b>Background</b> von Willebrand factor (vWF) plays an important role in platelet activation. CD40-CD40 ligand (CD40L) induced vWF release has been described in large vessels and cultured endothelium, but its role in the microcirculation is not known. Here, we studied whether CD40 is expressed in murine microvessels <i>in vivo</i>, whether CD40L induces platelet adhesion and leukocyte activation, and how deficiency of the vWF cleaving enzyme ADAMTS13 affects these processes.</p> <p> <b>Methods and Results</b> The role of CD40L in the formation of beaded platelet strings reflecting their adhesion to ultralarge vWF fibers (ULVWF) was analyzed in the murine cremaster microcirculation <i>in vivo</i>. Expression of CD40 and vWF was studied by immunohistochemistry in isolated and fixed cremasters. Microvascular CD40 was only expressed under inflammatory conditions and exclusively in venous endothelium. We demonstrate that CD40L treatment augmented the number of platelet strings, reflecting ULVWF multimer formation exclusively in venules and small veins. In ADAMTS13 knockout mice, the number of platelet strings further increased to a significant extent. As a consequence extensive thrombus formation was induced in venules of ADAMTS13 knockout mice. In addition, circulating leukocytes showed primary and rapid adherence to these platelet strings followed by preferential extravasation in these areas.</p> <p> <b>Conclusion</b> CD40L is an important stimulus of microvascular endothelial ULVWF release, subsequent platelet string formation and leukocyte extravasation but only in venous vessels under inflammatory conditions. Here, the lack of ADAMTS13 leads to severe thrombus formation. The results identify CD40 expression and ADAMTS13 activity as important targets to prevent microvascular inflammatory thrombosis.</p> | ||
| 700 | 1 | |a Wagner, Andreas H. |d 1963- |e VerfasserIn |0 (DE-588)1047559080 |0 (DE-627)778552381 |0 (DE-576)401158144 |4 aut | |
| 700 | 1 | |a Dietzel, Steffen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mannell, Hanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pircher, Joachim |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weckbach, Ludwig T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hecker, Markus |d 1960- |e VerfasserIn |0 (DE-588)1071693344 |0 (DE-627)826266037 |0 (DE-576)433260319 |4 aut | |
| 700 | 1 | |a Pohl, Ulrich |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Thrombosis and haemostasis |d Stuttgart : Thieme, 1976 |g 120(2020), 3, Seite 466-476 |h Online-Ressource |w (DE-627)302723188 |w (DE-600)1492370-1 |w (DE-576)079877362 |x 2567-689X |7 nnas |a Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice |
| 773 | 1 | 8 | |g volume:120 |g year:2020 |g number:3 |g pages:466-476 |g extent:11 |a Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice |
| 856 | 4 | 0 | |u https://doi.org/10.1055/s-0040-1702228 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://www.thieme-connect.de/DOI/DOI?10.1055/s-0040-1702228 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200420 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 1071693344 |a Hecker, Markus |m 1071693344:Hecker, Markus |d 50000 |d 53200 |e 50000PH1071693344 |e 53200PH1071693344 |k 0/50000/ |k 1/50000/53200/ |p 7 | ||
| 998 | |g 1047559080 |a Wagner, Andreas H. |m 1047559080:Wagner, Andreas H. |d 50000 |d 53200 |e 50000PW1047559080 |e 53200PW1047559080 |k 0/50000/ |k 1/50000/53200/ |p 2 | ||
| 999 | |a KXP-PPN1695006003 |e 3627497562 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 20.04.2020"],"person":[{"display":"Tahir, Sibgha","family":"Tahir","roleDisplay":"VerfasserIn","given":"Sibgha","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Wagner, Andreas H.","family":"Wagner","given":"Andreas H.","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Dietzel, Steffen","family":"Dietzel","role":"aut","given":"Steffen"},{"roleDisplay":"VerfasserIn","display":"Mannell, Hanna","family":"Mannell","role":"aut","given":"Hanna"},{"roleDisplay":"VerfasserIn","display":"Pircher, Joachim","family":"Pircher","given":"Joachim","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Weckbach, Ludwig T.","family":"Weckbach","role":"aut","given":"Ludwig T."},{"given":"Markus","role":"aut","roleDisplay":"VerfasserIn","display":"Hecker, Markus","family":"Hecker"},{"role":"aut","given":"Ulrich","family":"Pohl","display":"Pohl, Ulrich","roleDisplay":"VerfasserIn"}],"title":[{"title":"Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice","title_sort":"Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"id":{"doi":["10.1055/s-0040-1702228"],"eki":["1695006003"]},"language":["eng"],"physDesc":[{"extent":"11 S."}],"recId":"1695006003","name":{"displayForm":["Sibgha Tahir, Andreas H. Wagner, Steffen Dietzel, Hanna Mannell, Joachim Pircher, Ludwig T. Weckbach, Markus Hecker, Ulrich Pohl"]},"relHost":[{"id":{"doi":["10.1055/s-00035024"],"issn":["2567-689X"],"zdb":["1492370-1"],"eki":["302723188"]},"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"publisherPlace":"Stuttgart ; Stuttgart","dateIssuedKey":"1976","dateIssuedDisp":"1976-","publisher":"Thieme ; Schattauer"}],"recId":"302723188","pubHistory":["35.1976 -"],"disp":"Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout miceThrombosis and haemostasis","part":{"volume":"120","pages":"466-476","year":"2020","text":"120(2020), 3, Seite 466-476","extent":"11","issue":"3"},"note":["Gesehen am 15.06.2018"],"title":[{"title_sort":"Thrombosis and haemostasis","subtitle":"journal of the International Society on Thrombosis and Haemostasis","title":"Thrombosis and haemostasis"}],"type":{"bibl":"periodical","media":"Online-Ressource"}}],"origin":[{"dateIssuedKey":"2020","dateIssuedDisp":"[2020]"}]} | ||
| SRT | |a TAHIRSIBGHENDOTHELIA2020 | ||