Skip to main content
Log in

Phospholipase A2 Secretion During Intestinal Graft Ischemia

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The time-dependent appearance of phospholipaseA2 (PLA2) activity in thepreservation media of ischemic rat intestinal grafts isdescribed. In controls, Ca2+-dependent,secretory PLA2 activity accumulated rapidly during the first 6 hr of ischemia,followed by a linear increase for up to 48 hr. LDHlevels, by contrast, increased linearly throughout the48 hr of ischemia. Addition of inhibitors ofPLA2, cyclooxygenase, and lipooxygenase blocked accumulation ofPLA2, but not LDH. PX-13, a novelPLA2 inhibitor, was most effective: 40 μMinhibited release by 86%, while 25 μM indomethacin(cyclooxygenase blocker) or nordihydroguiaretic acid (lipooxygenaseblocker) inhibited 41 and 36%, respectively. Thatappearance of PLA2 activity, but not LDH, isattenuated by inhibitors of the eicosanoid cascadesuggests a secretory event rather than leakage from dying cells. Thesecreted PLA2 is most likely theproinflammatory sPLA2 that has beenimplicated as a stress-induced protein and priming agentin ischemia-reperfusion injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Sonnino RE, Pritchard T, Riddle JM: Limited survival of rat small bowel transplants preserved in University of Wisconsin solution for 48 hours. J Invest Surg 6(2):185-199, 1993

    Google Scholar 

  2. Mueller AR, Nalesnik MA, Langrehr JM, Rao PN, Snyder JT, Hoffman RA, Schraut WH: Evidence that small bowel preservation causes primarily basement membrane and endothelial rather than epithelial cell injury. Transplantation 56(6):1499-1504, 1993

    Google Scholar 

  3. Matsuda Y, Ogawa M, Sakamoto K, Yamashita S, Kanda A, Kohno M, Yoshida N, Nishijima J, Murata A, Mori T: Development of a radioimmunoassay for human group II phospholipase A2 and demonstration of postoperative elevation. Enzyme 45:200-208, 1991

    Google Scholar 

  4. Nevalainen TJ: Serum phospholipases A2 in inflammatory diseases. Clin Chem 39(12):2453-2459, 1993

    Google Scholar 

  5. Mansbach CM, Pieroni G, Verger R: Intestinal phospholipase, a novel enzyme. J Clin Invest 69:368-376, 1982

    Google Scholar 

  6. Otamiri T, Tagesson C: Role of Phospholipase A2 and oxygenated free radicals in mucosal damage after small intestinal ischemia and reperfusion. Am J Surg 157:562-566, 1989

    Google Scholar 

  7. Mansbach CM: Phospholipases: Old enzymes with new meaning. Gastroenterology 98(5):1369-1382, 1990

    Google Scholar 

  8. Anderson BO, Moore EE, Banerjee A: Phospholipase A2 regulates critical inflammatory mediators of multiple organ failure. J Surg Res 56(2):199-205, 1994

    Google Scholar 

  9. Fitzpatrick LR, Bostwick JS, Renzetti M, Pendleton RG, Decktor DL: Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat. Agents Action 30(3–4):393-402, 1990

    Google Scholar 

  10. Tordjman C, Coge F, Andre N, Rique H, Spedding M, Bonnet J: Characterization of cyclooxygenase 1 and 2 expression in mouse resident peritoneal macrophages in vitro; interactions of nonsteroidal anti-inflammatory drugs with COX2. Biochim Biophys Acta 1256(2):249-256, 1995

    Google Scholar 

  11. Koike K, Moore EE, Moore FA, Kim FJ, Carl VS, Banerjee A: Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion. Am J Physiol 268:G397-G403, 1995

    Google Scholar 

  12. Franson RC, Rosenthal MD: PX-52, a novel inhibitor of 14 kDa secretory and 85 kDa cytosolic phospholipases A2. In 3rd International Conference on Eicosanoids and Bioactive Lipids in Cancer, Inflammation and Radiation Injury. KV Honn, (ed). Dordrecht, Kluwer Academic Publishers, 1994, pp 357-365

    Google Scholar 

  13. Sonnino RE, Harmel RPJ: Technical aspects of intestinal transplantation in the rat. J Invest Surg 1(1):55-64, 1988

    Google Scholar 

  14. Sonnino RE, Franson R, Pigatt LA, Burchett S, Schrama A: Secretory phospholipase A2 levels in rat small bowel. J Invest Surg 9:313-319, 1996

    Google Scholar 

  15. Franson RC, Patriarca PL, Elsbach PJ: Phospholipid metabolism by phagocytic cells. PLA2s associated with rabbit PMN granules. J Lipid Res 15:380-388, 1974

    Google Scholar 

  16. Cahn RD, Kaplan NO, Levine L, Zwilling E: Nature and development of lactate dehydrogenases. Science 136:921, 1962

    Google Scholar 

  17. Dennis EA: Diversity of group types, regulation and function of phospholipase A2. J Biol Chem 269(18):13057-13061, 1994

    Google Scholar 

  18. Lambeau G, Ancian P, Nicolas J, Beiboers S, Moinier D, Verheij H, Lazdunski M: Structural elements of secretory phospholipase A2 involved in the binding to M-type receptors. J Biol Chem 270(10):5534-5540, 1995

    Google Scholar 

  19. Pfellschefler J, Schalwijk C, Briner V, van der Bosch H: Cytokine stimulated secretion of group II PLA2 by rat mesangial cells: Its contribution to arachidonic acid release and prostaglandin synthesis by cultured rat glomerular cells. J Clin Invest 92:2516-2523, 1994

    Google Scholar 

  20. Crowl R, Stoller T, Conroy R, Stoner C: Induction of PLA2 gene expression in human hepatoma by mediators of the acute phase response. J Biol Chem 264:2647-2651, 1991

    Google Scholar 

  21. Minami TH, Tojo Y, Shinomura T, Komatsubara Y, Matsuzawa Y, Okamoto M: Elevation of phospholipase A2 protein in sera of patients with Crohn's disease and ulcerative colitis. Am J Gastroenterol 88:1076-1080, 1993

    Google Scholar 

  22. Dorsam G, Harris L, Payne M, Fry M, Franson R: Development and use of ELISA to quantify type II phospholipase A2 in normal and uremic serum. Clin Chem 41(6):862-866, 1995

    Google Scholar 

  23. Musemeche CA, Baker JL, Feddersen RM: A model of intestinal ischemia in the neonatal rat utilizing superior mesenteric artery occlusion and intraluminal platelet-activating factor. J Surg Res 58:724-727, 1995

    Google Scholar 

  24. Clark M, Ozgier L, Conway T, Dispoto J, Crooke S, Bomalaski J: Cloning of PLA2 activating protein. Proc Natl Acad Sci USA 88:5418-5422, 1991

    Google Scholar 

  25. Levy O, Ooi C, Elsbach P, Doerfler M, Lehrer R, Weiss J: Antibacterial proteins of granulocytes differ in interaction with endotoxin. Comparison of bactericidal/permeability-increasing protein, p15s, and defensins. J Immunol 154(10):5403-5410, 1995

    Google Scholar 

  26. Zvaritch E, Lambeau G, Lazdunski M: Endocytic properties of the M-type 180-kDa receptor for secretory phospholipases A2. J Biol Chem 271(1):250-257, 1996

    Google Scholar 

  27. Sommers C, Bobbitt J, Bemis K, Snyder D: Porcine pancreatic phospholipase A2-induced contractions of guinea pig lung pleural strips. Eur J Pharmacol 216(1):87-96, 1992

    Google Scholar 

  28. Tohkin M, Kishino J, Ishaki J, Arita H: Pancreatic-type phospholipase A2 stimulates prostaglandin synthesis in mouse osteoblastic cells (MC3T3-E1) via a specific binding site. J Biol Chem 268(4):2865-2871, 1993

    Google Scholar 

  29. Kishino J, Kawamoto K, Ishizaki J, Verheij HM, Ohara O, Arita H: Pancreatic-type phospholipase A2 activates prostaglandin E2 production in rat mesangial cells by receptor binding reaction. J Biochem 117:420-424, 1995

    Google Scholar 

  30. Otamiri T: Quinacrine prevention of intestinal ischaemic mucosal damage is partly mediated through inhibition of intraluminal Phospholipase A2. Agents Actions 25(3–4):378-384, 1988

    Google Scholar 

  31. Otamiri T, Lindahl M, Tagesson C: Phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia in rats. Gut 29:484-494, 1988

    Google Scholar 

  32. Koike K, Moore EE, Moore FA, Carl VS, Pitman JM, Banerjee A: Phospholipase A2 inhibition decouples lung injury from gut ischemia-reperfusion. Surgery 112(2):173-180, 1992

    Google Scholar 

  33. Shen CY, Wang D, Chang ML, Hsu K: Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats. J Appl Physiol 78(1):225-231, 1995

    Google Scholar 

  34. Moore EE, Moore FA, Francoise RJ, Kim FJ, Biffl WL, Banerjee A: The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma 37(6):881-887, 1994

    Google Scholar 

  35. Santos AA, Browning JL, Scheltinga MR, Lynch EA, Brown EF, Lawton P, Chambers E, Dougas I, Benjamin CD, Dinarello CA, Wolff SM, Jacobs DO, Wilmore DW: Are events after endotoxemia related to circulating phospholipase A2? Ann Surg 219(2):183-192, 1994

    Google Scholar 

  36. Taguchi T, Zorychta E, Sonnino RE, Guttman FM: Function of smooth muscle and nerve after small intestinal transplantation in the rat: Effect of storing donor bowel in Eurocollins. J Pediatr Surg 24(7):634-638, 1989

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sonnino, R.E., Pigatt, L., Schrama, A. et al. Phospholipase A2 Secretion During Intestinal Graft Ischemia. Dig Dis Sci 42, 972–981 (1997). https://doi.org/10.1023/A:1018876717308

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018876717308

Navigation