Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion.
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Journal: 1993/November - Annals of Surgery
ISSN: 0003-4932
PUBMED: 8215636
Abstract:
OBJECTIVE
The role of polymorphonuclear neutrophils (PMN) was examined in local and remote organ injury after intestinal ischemia-reperfusion.
BACKGROUND
PMN have been found to mediate the local injury in low flow intestinal ischemia-reperfusion. However, in complete intestinal ischemia-reperfusion, prevention of PMN adhesion by monoclonal antibodies to CD11b and CD18 reduces remote but not local intestinal injury. The role of PMN was further investigated in this setting.
METHODS
In a rat model of 1-hour complete intestinal ischemia and 4-hour reperfusion. PMN were manipulated in the following four ways: (1) inhibition of oxygen-free radicals using manganese superoxide dismutase and catalase (SOD/CAT), (2) antagonism of PMN elastase using secretory leukocyte protease inhibitor (SLPI), (3) neutropenia using PMN antisera, and (4) inhibition of activation and adhesion using interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor binding protein (TNFbp). Lung injury was quantified by the pulmonary permeability index, which is the ratio of bronchoalveolar lavage to blood concentration of radiolabeled bovine serum albumin, and PMN sequestration by myeloperoxidase (MPO) activity. Liver injury was estimated by PMN counts using quantitative histologic examination and by serum glutamic pyruvic transaminase (SGPT). Local injury was quantified by MPO activity and histologic grading.
RESULTS
Neutropenia reduced the pulmonary permeability 80% from 11.0 +/- 0.5 x 10(-3) with saline treatment to 5.50 +/- 0.12 x 10(-3); IL-1ra, to 5.62 +/- 0.44 x 10(-3); and TNFbp, to 4.32 +/- 0.18 x 10(-3) (all p < 0.05). Pulmonary MPO rose from 0.03 +/- 0.01 U/g to 0.25 +/- 0.03 U/g (p < 0.05). This was reduced by neutropenia, 0.01 +/- 0.003 U/g, but not by inhibition of oxygen-free radicals or PMN elastase. IL-1ra inhibited PMN sequestration, reducing MPO to 0.12 +/- 0.01 (p < 0.05). Liver injury was 60% dependent on PMN. Ischemia-reperfusion increased SGPT from 20.3 +/- 0.7 IU/L in the sham-treated animals to 97.0 +/- 3.1 IU/L in the experimental animals. Neutropenia reduced this to 48.1 +/- 3.9 IU/L; IL-1ra, to 44.7 +/- 3.7 IU/L; SOD/CAT, to 64.0 +/- 3.38 IU/L; and SLPI, to 57.1 +/- 3.4 IU/L (p < 0.05 in all cases). Local injury was severe and unaffected by manipulation of the PMN.
CONCLUSIONS
These data suggest that PMN and their products mediate most of the lung, part of the liver, and none of the local gut injury after intestinal ischemia-reperfusion.
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Ann Surg 218(4): 444-454
PMID: 8215636

Neutrophil and nonneutrophil-mediated injury in intestinal ischemia-reperfusion.

Abstract

OBJECTIVE: The role of polymorphonuclear neutrophils (PMN) was examined in local and remote organ injury after intestinal ischemia-reperfusion. SUMMARY BACKGROUND DATA: PMN have been found to mediate the local injury in low flow intestinal ischemia-reperfusion. However, in complete intestinal ischemia-reperfusion, prevention of PMN adhesion by monoclonal antibodies to CD11b and CD18 reduces remote but not local intestinal injury. The role of PMN was further investigated in this setting. METHODS: In a rat model of 1-hour complete intestinal ischemia and 4-hour reperfusion. PMN were manipulated in the following four ways: (1) inhibition of oxygen-free radicals using manganese superoxide dismutase and catalase (SOD/CAT), (2) antagonism of PMN elastase using secretory leukocyte protease inhibitor (SLPI), (3) neutropenia using PMN antisera, and (4) inhibition of activation and adhesion using interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor binding protein (TNFbp). Lung injury was quantified by the pulmonary permeability index, which is the ratio of bronchoalveolar lavage to blood concentration of radiolabeled bovine serum albumin, and PMN sequestration by myeloperoxidase (MPO) activity. Liver injury was estimated by PMN counts using quantitative histologic examination and by serum glutamic pyruvic transaminase (SGPT). Local injury was quantified by MPO activity and histologic grading. RESULTS: Neutropenia reduced the pulmonary permeability 80% from 11.0 +/- 0.5 x 10(-3) with saline treatment to 5.50 +/- 0.12 x 10(-3); IL-1ra, to 5.62 +/- 0.44 x 10(-3); and TNFbp, to 4.32 +/- 0.18 x 10(-3) (all p < 0.05). Pulmonary MPO rose from 0.03 +/- 0.01 U/g to 0.25 +/- 0.03 U/g (p < 0.05). This was reduced by neutropenia, 0.01 +/- 0.003 U/g, but not by inhibition of oxygen-free radicals or PMN elastase. IL-1ra inhibited PMN sequestration, reducing MPO to 0.12 +/- 0.01 (p < 0.05). Liver injury was 60% dependent on PMN. Ischemia-reperfusion increased SGPT from 20.3 +/- 0.7 IU/L in the sham-treated animals to 97.0 +/- 3.1 IU/L in the experimental animals. Neutropenia reduced this to 48.1 +/- 3.9 IU/L; IL-1ra, to 44.7 +/- 3.7 IU/L; SOD/CAT, to 64.0 +/- 3.38 IU/L; and SLPI, to 57.1 +/- 3.4 IU/L (p < 0.05 in all cases). Local injury was severe and unaffected by manipulation of the PMN. CONCLUSIONS: These data suggest that PMN and their products mediate most of the lung, part of the liver, and none of the local gut injury after intestinal ischemia-reperfusion.

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Selected References

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Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Copyright notice
Abstract
OBJECTIVE: The role of polymorphonuclear neutrophils (PMN) was examined in local and remote organ injury after intestinal ischemia-reperfusion. SUMMARY BACKGROUND DATA: PMN have been found to mediate the local injury in low flow intestinal ischemia-reperfusion. However, in complete intestinal ischemia-reperfusion, prevention of PMN adhesion by monoclonal antibodies to CD11b and CD18 reduces remote but not local intestinal injury. The role of PMN was further investigated in this setting. METHODS: In a rat model of 1-hour complete intestinal ischemia and 4-hour reperfusion. PMN were manipulated in the following four ways: (1) inhibition of oxygen-free radicals using manganese superoxide dismutase and catalase (SOD/CAT), (2) antagonism of PMN elastase using secretory leukocyte protease inhibitor (SLPI), (3) neutropenia using PMN antisera, and (4) inhibition of activation and adhesion using interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor binding protein (TNFbp). Lung injury was quantified by the pulmonary permeability index, which is the ratio of bronchoalveolar lavage to blood concentration of radiolabeled bovine serum albumin, and PMN sequestration by myeloperoxidase (MPO) activity. Liver injury was estimated by PMN counts using quantitative histologic examination and by serum glutamic pyruvic transaminase (SGPT). Local injury was quantified by MPO activity and histologic grading. RESULTS: Neutropenia reduced the pulmonary permeability 80% from 11.0 +/- 0.5 x 10(-3) with saline treatment to 5.50 +/- 0.12 x 10(-3); IL-1ra, to 5.62 +/- 0.44 x 10(-3); and TNFbp, to 4.32 +/- 0.18 x 10(-3) (all p < 0.05). Pulmonary MPO rose from 0.03 +/- 0.01 U/g to 0.25 +/- 0.03 U/g (p < 0.05). This was reduced by neutropenia, 0.01 +/- 0.003 U/g, but not by inhibition of oxygen-free radicals or PMN elastase. IL-1ra inhibited PMN sequestration, reducing MPO to 0.12 +/- 0.01 (p < 0.05). Liver injury was 60% dependent on PMN. Ischemia-reperfusion increased SGPT from 20.3 +/- 0.7 IU/L in the sham-treated animals to 97.0 +/- 3.1 IU/L in the experimental animals. Neutropenia reduced this to 48.1 +/- 3.9 IU/L; IL-1ra, to 44.7 +/- 3.7 IU/L; SOD/CAT, to 64.0 +/- 3.38 IU/L; and SLPI, to 57.1 +/- 3.4 IU/L (p < 0.05 in all cases). Local injury was severe and unaffected by manipulation of the PMN. CONCLUSIONS: These data suggest that PMN and their products mediate most of the lung, part of the liver, and none of the local gut injury after intestinal ischemia-reperfusion.
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