News From The Journal Of Clinical Investigation : Aug. 21, 2008

Main Category: Blood / Hematology
Also Included In: Biology / Biochemistry
Article Date: 23 Aug 2008 - 1:00 PDT

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Molecular insight into one form of the bleeding disorder von Willebrand disease

Individuals with von Willebrand disease (vWD) are at increased risk of bleeding compared with healthy individuals, for example, they tend to bruise more easily and suffer more nosebleeds and bleeding gums. There are four types of inherited vWD, and type 2B vWD is caused by genetic mutations that result in the generation of mutant forms of the protein vWF that differ from normal vWF in a region of the protein known as the A1 domain. A team of researchers at Georgia Institute of Technology, Atlanta, and Oklahoma Medical Research Foundation, Oklahoma City, has now characterized in great molecular detail how the function of mutant forms of vWF found in individuals with type 2B vWD and normal vWF differ, providing insight into why these mutant proteins cause an increased risk of bleeding. In an accompanying commentary, Michael Berndt, at the University College Cork, Ireland, and Robert Andrews, at Monash University, Australia, discuss the importance of these results.

TITLE: Platelet glycoprotein Ib-alpha forms catch bonds with human WT vWF but not with type 2B von Villebrand disease vWF

AUTHOR CONTACT:

Cheng Zhu
Georgia Institute of Technology, Atlanta, Georgia, USA.

Roger P. McEver
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=35754

ACCOMPANYING COMMENTARY

TITLE: Platelet adhesion: a game of catch and release

AUTHOR CONTACT:
Michael C. Berndt
University College Cork, Cork, Republic of Ireland.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36883

Insight into the physiologic role of the blood protein Factor XII finally revealed

The formation of a blood clot is the culmination of a series of events that involve a number of proteins in the bloodstream, including Factor XI, which is one of the proteins activated early on in this cascade of events. Surprisingly, Factor XI is activated in different ways in the body and in a glass test tube. In a glass test tube, Factor XI is activated by a protein known as Factor XII, which is itself activated when it comes into contact with the glass. However, Factor XII plays no role in Factor XI activation in the body and its physiologic function and mechanism of activation have not been determined.

New data, generated by Martijn Gebbink and colleagues, at the University Medical Center Utrecht, The Netherlands, have identified the aggregates of misfolded proteins present in the blood of individuals with systemic amyloidosis (a disease in which misfolded blood proteins are abnormally deposited in organs and/or tissues, causing disease) as activators of Factor XII. Interestingly, activation of Factor XII by isolated misfolded proteins and misfolded proteins in the blood of individuals with systemic amyloidosis did not trigger the cascade of events that lead to blood clot formation. Rather, it triggered another series of events known as the kallikrein-kinin system, which influences the inflammatory response. In an accompanying commentary, Alvin Schmaier, at Case Western Reserve University, Cleveland, discusses these results in the context of previously published data.

TITLE: Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation

AUTHOR CONTACT:
Martijn F.B.G. Gebbink
University Medical Center Utrecht, Utrecht, The Netherlands
.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35424

ACCOMPANYING COMMENTARY

TITLE: The elusive physiologic role of Factor XII

AUTHOR CONTACT:
Alvin H. Schmaier
Case Western Reserve University, Cleveland, Ohio, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36617

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Source: Karen Honey
Journal of Clinical Investigation

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