Insight Into Physiologic Role Of Blood Protein Factor XII Finally Revealed

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.