title: Extracellular histone induces plasma hyaluronan-binding protein (factor VII activating protease) activation in vivo.
abstract: Plasma hyaluronan-binding protein (PHBP), an activator of factor VII and prourokinase, is a serine protease circulating as a single-chain proenzyme (pro-PHBP). Pro-PHBP converts to the active two-chain form through autoproteolysis, and effectors that modulate autoactivation can regulate PHBP-mediated processes. Here, we show that histone promotes pro-PHBP autoactivation in vivo. Histone bound to pro-PHBP and promoted intermolecular pro-PHBP binding. Histone-mediated pro-PHBP activation in plasma leads to the formations of bradykinin and PHBP-α(2)-antiplasmin complex as well as histone degradation. Pro-PHBP activation was observed in the circulation of mice after injection of histone or lipopolysaccharide, which induced septic response accompanying extracellular histone release. Our results suggest pathophysiological relevance of histone-dependent pro-PHBP activation in hyperinflammatory process.
authors: Department of Applied Biological Science, Tokyo Noko University, 3-5-8 Saiwaicho, Fuchu, Tokyo 183-8509, Japan.
authors: Shingo
authors: S
authors: Yamamichi
authors: Yukari
authors: Y
authors: Fujiwara
authors: Tadashi
authors: T
authors: Kikuchi
authors: Miki
authors: M
authors: Nishitani
authors: Yasuhiko
authors: Y
authors: Matsushita
authors: Keiji
authors: K
authors: Hasumi