Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury.
The objective of this work was to test the hypothesis that Intraluminal serine proteases are involved in trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury. Male Sprague-Dawley rats were administrated the serine protease inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, Nafamostat) either intraluminally into the gut or intravenously after a laparotomy (trauma) and then subjected to 90 min of hemorrhagic shock (T/HS) or sham shock (T/SS). Intestinal and lung injury was assessed at 3 h after resuscitation with Ringer's lactate solution. In a second set of experiments, mesenteric lymph was collected from the groups of rats subjected to T/HS or T/SS and its ability to activate normal neutrophils was tested. Lung permeability, pulmonary myeloperoxidase levels, and the bronchoalveolar lavage fluid protein to plasma protein ratio were increased after T/HS but were significantly decreased in the T/HS rats receiving intraluminal (P < 0.05), but not intravenous, nafamostat. Likewise, T/HS-induced intestinal villus injury was less in the nafamostat-treated shock rats (P < 0.05). Last, the ability of T/HS mesenteric lymph to increase PMN CD11b expression or prime neutrophils for an augmented respiratory burst was significantly reduced by the intraluminal administration of nafamostat. Because intraluminal nafamostat reduced T/HS-induced gut and lung injury as well as the neutrophil activating ability of intestinal T/HS lymph, the presence of serine proteases in the ischemic gut may play an important role in T/HS-induced gut and hence lung injury.
Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Edwin A
EA
Deitch
Han Ping
HP
Shi
Qi
Q
Lu
Eleonora
E
Feketeova
Da Zhong
DZ
Xu
D000818:Animals; D001550:Benzamidines; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006146:Guanidines / Q000633:toxicity; D007082:Ileum / Q000293:injuries* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000633:toxicity; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology*
D001550:Benzamidines; D015815:Cell Adhesion Molecules; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C032855:nafamostat