Damage to the intestinal mucosal barrier sustained during the compensated stages of shock may result in bacterial translocation and systemic accumulation of toxins, leading to sepsis and multiple organ failure. Neutrophils are known to be an important component of endotoxin and cytokine-induced tissue injury. The purpose of this study, therefore, was to test the hypothesis that neutrophil infiltration and MPO production accompany endotoxin and TNFα induced intestinal mucosal dysfunction.
To evaluate mucosal dysfunction, jejunal blood-to-lumen clearances of chromium 51-labeled ethylenediaminetetraacetate (51Cr-EDTA) were measured in cats administered fetal calf serum (controls), endotoxin, TNFα, or polyclonal anti-TNFα antibody followed by endotoxin. Neutrophil accumulation in the jejunal mucosa was evaluated by histologic enumeration and measurement of jejunal myeloperoxidase (MPO) activity.
Endotoxin and TNFα induced mucosal dysfunction in the proximal jejunum is accompanied by neutrophil accumulation in the jejunal mucosa as indicated by histologic enumeration and increased MPO activity. Pretreatment with anti-TNFα polyclonal antibody significantly decreased endotoxin-induced increases in jejunal MPO activity. The results of this study support the contribution of neutrophils to endotoxin and TNFα induced mucosal dysfunction.
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References
1.
O'Dwyer S., Michie H., Ziegler T., Revhaug A., Smith R., Wilmore D.A single dose of endotoxin increases intestinal permeability in healthy humans . Arch Surg1988; 128: 1459-1464.
2.
Deitch E., Berg R., Specian R.Endotoxin promotes the translocation of bacteria from the gut. Arch Surg1987; 122: 185-190.
3.
Go L., Healey P., Watkins S., Simmons R., Rowe M.The effect of endotoxin on intestinal mucosal permeability to bacteria in vitro. Arch Surg1995; 130: 53-58.
4.
Jackman B., Eades S., Moore J., Harmon B.Differential effects of an infusion of endotoxin on proximal and distal feline jejunal permeability. J Endotoxin Res1996 ; 3: 77-86.
5.
Mueller P., Eades S., Moore J., Barton M.Contribution of tumor necrosis factor-alpha to endotoxin-induced mucosal dysfunction . J Endotoxin Res1996; 3: 323-332.
6.
Fink M.Gastrointestinal mucosal injury in experimental models of shock, trauma and sepsis. Crit Care Med1991; 19: 627-641.
7.
Z Debets J., Kampmeijer L., Van Der Linden M., Buurman W., Van Der Linden C.Plasma tumor necrosis factor and mortality in critically ill septic patients . Crit Care Med1989; 17: 489-492.
8.
Hesse D., Tracey K., Yuman F. et al. Cytokine appearance in human endotoxemia and primate bacteremia . Surg Gynecol Obstet1988; 166: 147-153.
9.
Michie H., Manogue K., Spriggs D. et al. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med1988; 318: 1481-1486.
10.
Tracey K., Beutler J., Lowry S.F., et al.. Shock and tissue injury induced by recombinant human cachectin . Science1986; 234: 470-474.
11.
Tracey K., Lowry S.The role of cytokine mediators in septic shock. Adv Surg1990; 23: 21-56.
12.
Hewett J., Schultze A., VanCise S., Roth R. Neutrophil depletion protects against liver injury from bacterial endotoxin. Lab Invest1992; 66: 347-361.
Matsuda T., Rubinstein L., Robbins R., Koyama S., Joyner W., Rennard S.Role of neutrophils in endotoxin-mediated microvascular injury in hamsters . J Appl Physiol1991; 71: 307-313.
15.
Kozol R.Neutrophil recruitment to the gastrointestinal tract. J Surg Res1992; 53: 310-315.
16.
Grisham M., Hernandez L., Granger D.Xanthine oxidase and neutrophil infiltration in intestinal ischemia . Am J Physiol1986; 251: G567-G574.
17.
Grisham M., Granger D.Neutrophil-mediated mucosal injury. Role of reactive oxygen metabolites . Dig Dis Sci1988; Suppl. 33: 6S—15S.
18.
Powell S., Tortolani A.Recent advances in the role of reactive oxygen intermediates in ischemic injury I. Evidence demonstrating presence of reactive oxygen intermediates; II. Role of metals in site-specific formation of radicals. J Surg Res1992; 53: 417-429.
19.
Musemeche C. , Pizzini R., Andrassy R.Intestinal ischemia in the newborn: the role of intestinal maturation. J Surg Res1993; 55: 595-598.
20.
Grisham M., Benoit J., Granger D.Assessment of leukocyte involvement during ischemia-reperfusion of intestine . Methods Enzymol1990; 186: 729-742.
21.
Krawisz J., Sharon P., Stenson W.Quantitive assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterolgy1984; 87: 1344-1350.
22.
Jaeschke H. , Farhood A., Smith C.Neutrophil-induced liver cell injury in endotoxic shock is a CD 1b/CD18-dependent mechanism. Am J Physiol1991; 261: G1051-G1056.
23.
Mathison J. , Wolfson E., Ulevitch R.Participation of tumor necrosis factor in the mediation of Gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest1988; 81: 1925-1937.
24.
Thomas J., Harlan J., Rice C., Winn R.Role of leukocyte CD 11 /CD 18 complex in endotoxic and septic shock in rabbits . J Appl Physiol1992; 73: 1510-1516.
25.
Richter J., NGSikorski J., Olsson L., Andersson T.Tumor necrosis factor-induced degranulation in adherent neutrophils is dependent on CD 11 b/CD 18-integrin-triggered oscillations of cytosolic free Ca2+. Proc Natl Acad Sci USA1990; 87: 9472-9476.
26.
Tracey K.Tumor necrosis factor (cachectin) in the biology of septic shock syndrome . Circ Shock1991; 35: 123-128.
27.
Bauldry S., McCall C., Cousart S.Bass D.Tumor necrosis factor-α priming of phospholipase A2 activation in human neutrophils: an alternative mechanism of priming. J Immunol1991; 146: 1277-1285.
28.
Berkow R., Wang D., Larrick J. et al. Enhancement of neutrophil superoxide production by preincubation with recombinant human tumor necrosis Factor. J Immunol1987; 139: 3783-3791.
29.
Nathan C., Srimal S., Farber C. et al. Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins. J Cell Biol1989 ; 109: 1341-1349.
30.
Cerasoli F. , McKenna P., Rosolia D., Albertine K., Peters S., Gee M.Superoxide anion release from blood and bone marrow neutrophils is altered by endotoxemia. Circ Res1990; 67: 154-165.
31.
Smedly L., Tonnesen M., Sandhaus R. et al. Neutrophil-mediated injury to endothelial cells: enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest1986; 77: 1233-1243.
32.
Caty M., Guice K., Oldham K., Remick D., Kunkel S.Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion. Ann Surg1990; 212: 694-698.
33.
Volmer K., Alberts J., Carper H., Mandell G.Tumor necrosis factor-alpha decreases neutrophil chemotaxis to n-formyl-1-methionyl-1-leucyl-1-phenylalanine: analysis of single cell movement. J Leukoc Biol1992; 52: 630-636.
34.
Welbourn R. , Goldman G., O'Riordain M. et al. Role of tumor necrosis factor as mediator of lung injury following lower torso ischeniia . J Appl Physiol1991; 70: 2645-2649.
35.
Zimmerman B. , Guillory D., Grisham M., Gaginella T., Granger D.Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. Gastroenterology1990; 99: 1358-1363.
36.
Kubes P., Arfors K., Granger N.Platelet-activating factor-induced mucosal dysfunction: role of oxidants and granulocytes. Am J Physiol1991; 260: G965-G971.
37.
Eberhart C. , Dubois R.Eicosanoids and the gastrointestinal tract . Gastroenterology1995; 109: 285-301.
38.
Ogeltree M. , O'Keefe E., Durham S., Rubin B., Aberg G.Gastroprotective effects of thromboxane receptor antagonists. J Pharmacol Exp Ther1992; 263: 374-380.
39.
Cook J., Li E., Spicer K., Wise W., Halushka P.Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock. Circ Shock1990; 32: 209-218.
40.
Lefer A.Leukotrienes as mediators of ischemia and shock. Biochem Pharmacol1986; 35: 355-376.
