Early complement system activation and neutrophil priming in acute pancreatitis: participation of trypsin.
BACKGROUND
It is known that the pancreatic enzyme trypsin can cleave components of the complement system, producing the chemokines C3a and C5a. In the setting of experimental acute pancreatitis, we analyzed the contribution of serum trypsin to systemic complement activation and its importance in neutrophil lung sequestration, an early event in acute pancreatitis.


METHODS
Cerulein was infused into Lewis rats to produce mild edematous acute pancreatitis. Soluble complement receptor, sCR1, was used to block complement activation.


RESULTS
Induction of acute pancreatitis was confirmed by the serum levels of amylase and trypsin and by histologic studies. A correlation was found between serum total complement activity and the trypsin level (r = -0.884). Whole lung tissue myeloperoxidase activity was high in rat lungs at t = 4 hours, indicating accumulation of neutrophils. The sCR-1-treated group showed significantly lower levels. Flow cytometry of neutrophils incubated with serum from rats with pancreatitis showed significantly higher CD11b/CD18 expression than that after incubation with serum from control or sCR-1-treated rats. Until t = 12 hours, no change in the lung wet to dry weight ratio or bronchoalveolar fluid cytology was observed, indicating no functional enhancement of neutrophils that had accumulated in the lungs.


CONCLUSIONS
The present results demonstrate the important role of trypsin in systemic complement activation early in the course of acute pancreatitis. The resulting central production of chemotaxins causes priming of circulating neutrophils and subsequent lung sequestration. These events can be at least partially reversed by sCR-1 treatment.
Acioli
J M
JM
First Department of Surgery, Shinshu University School of Medicine, Matsumoto City, Japan.
Isobe
M
M
Kawasaki
S
S
D000208:Acute Disease; D000681:Amylases / Q000097:blood*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018821:CD18 Antigens / Q000097:blood; D003167:Complement Activation; D005434:Flow Cytometry; D008168:Lung / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000097:blood* / Q000473:pathology*; D009195:Peroxidase / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D012044:Regression Analysis; D013997:Time Factors; D014357:Trypsin / Q000097:blood* / Q000378:metabolism
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D009195:Peroxidase; D000681:Amylases; D014357:Trypsin