Experimental necrotizing enterocolitis: the role of polymorphonuclear neutrophils
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C Musemeche1, M Caplan, W Hsueh
1Children's Memorial Hospital, Chicago, IL.
Abstract:
Polymorphonuclear neutrophils (PMNs) play an important role in inflammation. Activated PMNs adhere to the vascular wall and release reactive oxygen radicals and enzymes, producing vascular injury. In the present study, we investigated whether PMNs play an important role in the pathogenesis of experimental necrotizing enterocolitis (NEC). NEC was induced in rats using platelet activating factor (PAF, 1 microgram/kg) and bacterial endotoxin (LPS, 1 mg/kg) intravenously. Neutropenia was accomplished by parenteral injection of Vinblastine (VB, 0.75 mg/kg) 4 days before the experiment to deplete the total white blood cell (WBC) and neutrophil counts. The animals were divided into 4 groups: (1) 1 microgram/kg PAF; (2) 1 mg/kg LPS; (3) 1 microgram/kg PAF + 1 mg/kg LPS; and (4) PMN depleted, 1 microgram/kg PAF + 1 mg/kg LPS. Combined administration of PAF and LPS produced prolonged hypotension (blood pressure 53.5 +/- 13.8 mm Hg at 2 hours), leukopenia (4,062 +/- 497.4), hemoconcentration (hematocrit 44.5% +/- 1.1%), reduced intestinal perfusion (74% +/- 13.3%), and segmental bowel necrosis. However, in VB-treated animals combined PAF + LPS induced only mild hypotension (84.3 +/- 9.2 mm Hg at 2 hours) and no hemoconcentration. In these animals the intestinal perfusion was normal, no bowel necrosis was observed, and the intestinal myeloperoxidase activity (.0034 +/- .0017 U/g tissue) was significantly lower than that of the nondepleted group (.0075 +/- .0012 U/g tissue). We conclude that the presence of neutrophils and/or neutrophil products play a major role in the pathogenesis of NEC.
Insights
Neutrophils significantly contribute to necrotizing enterocolitis (NEC) development. Depleting neutrophils in rats reduced NEC severity, indicating their crucial role in this condition.
Area of Science:
- Immunology
- Gastroenterology
- Pathology
Background:
- Polymorphonuclear neutrophils (PMNs) are key mediators of inflammation and vascular injury.
- The role of PMNs in the pathogenesis of experimental necrotizing enterocolitis (NEC) requires further investigation.
Purpose of the Study:
- To investigate the role of PMNs in the pathogenesis of experimental NEC.
- To determine if neutrophil depletion affects NEC development and severity.
Main Methods:
- Experimental NEC was induced in rats using platelet-activating factor (PAF) and bacterial endotoxin (LPS).
- Neutropenia was achieved by administering Vinblastine (VB) to deplete white blood cells and neutrophils.
- Animals were divided into groups receiving PAF, LPS, combined PAF+LPS, or combined PAF+LPS with prior VB treatment.
Main Results:
- Combined PAF and LPS administration resulted in severe NEC, characterized by hypotension, leukopenia, hemoconcentration, reduced intestinal perfusion, and bowel necrosis.
- In VB-treated (neutropenic) animals, combined PAF+LPS induced only mild hypotension and no hemoconcentration or bowel necrosis.
- Intestinal perfusion was normal, and myeloperoxidase activity was significantly lower in neutropenic animals compared to the non-depleted group.
Conclusions:
- Neutrophils play a major role in the pathogenesis of experimental necrotizing enterocolitis.
- Neutrophil presence and/or their products are critical for the development of NEC-induced vascular injury and bowel necrosis.