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.