Sartor R B, DeLa Cadena R A, Green K D, Stadnicki A, Davis S W, Schwab J H, Adam A A, Raymond P, Colman R W
Department of Medicine, University of North Carolina, Chapel Hill, USA.
Gastroenterology. 1996 May;110(5):1467-81. doi: 10.1053/gast.1996.v110.pm8613052.
BACKGROUND & AIMS: Crohn's disease is characterized by unrestrained inflammation with a genetic component. Genetic susceptibility and activation of the kalli-krein-kinin (contact) system were investigated in experimental enterocolitis and extraintestinal inflammation induced by bacterial polymers.
Kinetics of inflammation in inbred Lewis and Buffalo rats injected subserosally with peptidoglycan-polysaccharide polymers were correlated with in vivo and in vitro activation of the contact system.
Lewis rats had a biphasic course of enterocolitis. Acute inflammation peaked 1 day after injection, gradually decreasing until day 14 when intestinal inflammation spontaneously reactivated and persisted for 16 weeks, accompanied by arthritis, granulomatous hepatitis, anemia, and leukocytosis. Self-limited acute enterocolitis in Buffalo rats resolved by 24 days without extraintestinal involvement. Consumption of the precursor proteins prekalli-krein and high-molecular-weight kininogen indicated activation of the plasma contact system in Lewis rats and closely correlated with chronic intestinal inflammation. Contact system activation did not occur in Buffalo rats, even during acute inflammation. In vitro studies showed a decreased rate of kininogen cleavage in Buffalo plasma.
Selective in vivo and in vitro activation of the contact system in susceptible Lewis rats suggests that this pathway is one determinant of genetic susceptibility to granulomatous enterocolitis and systemic complications.
克罗恩病的特征是存在遗传因素导致的不受控制的炎症。在由细菌聚合物诱导的实验性小肠结肠炎和肠外炎症中，研究了遗传易感性和激肽释放酶-激肽（接触）系统的激活情况。
将肽聚糖-多糖聚合物经浆膜下注射到近交系Lewis大鼠和布法罗大鼠体内，炎症动力学与接触系统的体内外激活情况相关联。
Lewis大鼠的小肠结肠炎呈双相病程。急性炎症在注射后1天达到高峰，逐渐下降，直到第14天肠道炎症自发重新激活并持续16周，同时伴有关节炎、肉芽肿性肝炎、贫血和白细胞增多。布法罗大鼠的自限性急性小肠结肠炎在24天时消退，无肠外受累。前体蛋白前激肽释放酶和高分子量激肽原的消耗表明Lewis大鼠血浆接触系统被激活，且与慢性肠道炎症密切相关。布法罗大鼠即使在急性炎症期间也未发生接触系统激活。体外研究显示布法罗大鼠血浆中激肽原裂解速率降低。
在易感的Lewis大鼠体内和体外选择性激活接触系统表明，该途径是肉芽肿性小肠结肠炎和全身并发症遗传易感性的一个决定因素。
