Compartmentalization of the protease-antiprotease balance in early severe acute pancreatitis.
OBJECTIVE
To assess the balance between trypsin and protease inhibitors simultaneously in the systemic circulation and in the thoracic lymph and peritoneal exudate.


METHODS
Twenty patients with early severe acute pancreatitis were studied. Enzymatically active and immunoreactive trypsin in conjunction with its major inhibitors were measured in the 3 compartments at the onset of end-organ failure(s). The molecular forms of trypsin were determined in the lymph and ascites by gel filtration chromatography to separate trypsinogen and free-and inhibitor-bound trypsin.


RESULTS
Both enzymatically active trypsin and immunoreactive trypsin levels were highest in ascites and lymph compared with the systemic circulation. Intracompartmental alpha1- protease inhibitor gradient moved in the opposite direction, whereas alpha2 macroglobulin concentration was highest in ascites and lowest in the lymph. Although most of the enzymatically and immunoreactive material in ascites and lymph consisted of trypsin complexed with alpha2 macroglobulin and trypsinogen, respectively, free active trypsin was detected in more than 80% of the samples.


CONCLUSIONS
In patients with early severe acute pancreatitis, there is a significant trypsinogen activation resulting in protease-antiprotease imbalance and thereby free enzymatically active trypsin in the 2 body fluid compartments in close vicinity to the inflammatory process. This may be involved in the pathophysiology of local and distant tissue damage.
Dugernier
Thierry
T
Department of Intensive Care, St. Luc University Hospital, Brussels, Belgium. thierry.dugernier@skynet.be
Laterre
Pierre-François
PF
Reynaert
Marc
M
Deby-Dupont
Ginette
G
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001201:Ascites / Q000201:enzymology*; D001825:Body Fluid Compartments; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008196:Lymph / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D012720:Severity of Illness Index; D014357:Trypsin / Q000378:metabolism*; D014362:Trypsinogen / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; D014362:Trypsinogen; D010447:Peptide Hydrolases; D014357:Trypsin