Experimental necrotizing enterocolitis: The role of polymorphonuclear neutrophils

Musemeche, Catherine A.; Caplan, Michael S.; Hsueh, Wei; Sun, Xiaoming; Kelly, Anthony

doi:10.1016/0022-3468(91)90671-f

Cited by 42 publications

(41 citation statements)

References 6 publications

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“…These findings are consistent with the view that endogenous NO may promote microvascular integrity and inhibit leukocyte adherence and emigration, thereby limiting PAF-induced bowel injury. Previous observations (5,25). as well as the present study, have shown a positive correlation between neutrophil infiltration into the bowel and development of intestinal injury.…”

Section: Discussionmentioning

confidence: 61%

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

1993

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ABSTRACT. Platelet-activating factor (PAF) causes bowel necrosis in animal models that is histologically identical to that seen in neonatal necrotizing enterocolitis, but little is known about endogenous mechanisms that might protect against PAF-induced bowel injury. We hypothesized that endogenous nitric oxide might represent such a protective mechanism. Adult male Sprague-Dawley rats were pretreated with 2.5 mg/kg NC-nitro-L-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, and given injections of 1.5 pg/kg PAF 15 min later. Animals treated with normal saline placebo, L-NAME alone, and PAF alone were also studied. Superior mesenteric artery blood flow and blood pressure were continuously recorded. At the end of 2 h or upon death of the animal, hematocrit was measured and intestinal samples were taken for histologic examination and determination of myeloperoxidase activity, a measure of intestinal neutrophil content. Compared with animals given PAF alone, animals pretreated with L-NAME followed by PAF developed significantly worse bowel injury (median injury scores: 2.5 versus 0.5, p = 0.005), hemoconcentration (final hematocrit 65.2 f 2.0% versus 53.9 f 1.0%, p < 0.001), and intestinal myeloperoxidase activity (12.45 f 1.94 U/g versus 6.51 + 0.57 U/g, p < 0.01). The last two effects were further accentuated when 10 mg/kg L-NAME was given before PAF. Treatment with sodium nitroprusside, a nitric oxide donor, for 10 min before and after PAF administration reversed the effects of L-NAME. Animals pretreated with phenylephrine rather than L-NAME did not develop worse injury than animals treated with PAF alone despite comparable reductions in superior mesenteric blood flow before PAF treatment. Treatment with superoxide dismutase and catalase did not ameliorate the effects of L-NAME on PAF-induced injury, hemoconcentration, and neutrophil infiltration into the bowel. We conclude that endogenous nitric oxide defends against PAF-induced bowel injury by antagonizing certain immediate effects of PAF, particularly those leading to capillary leakage and neutrophil infiltration into the bowel. Our studies also suggest that the mechanism of action does not involve vasodilatation or scavenging of oxygen radicals. (Pediatr Res 34: 222-228,1993) Abbreviations NO, nitric oxide PAF, platelet-activating factor SOD, superoxide dismutase CAT, catalase

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Section: Discussionmentioning

confidence: 61%

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

1993

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“…Hence, intestinal epithelial expression patterns of TLR-4 in the presence of altered intestinal flora may result in a variety of local responses, including altered bacterial translocation, gut homeostasis, and induction of cytokine pathways (71,81). Indeed, the administration of LPS to mice replicates the findings of human NEC (82,83). In mouse models of colitis and NEC, TLR-4 knockout mice have reduced inflammatory infiltrates when compared with wild-type mice (84).…”

Section: Bacteria and Their Products In The Pathogenesis Of Necmentioning

confidence: 96%

Understanding the Susceptibility of the Premature Infant to Necrotizing Enterocolitis (NEC)

et al. 2008

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Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency encountered in the neonatal intensive care unit. Despite advances in neonatal care, NEC remains a leading cause of morbidity and mortality among premature infants. Epidemiologic studies have identified multiple factors that increase an infant's risk for the development of NEC, although premature birth, bacterial colonization, and enteral feeding are thought to play central roles in disease pathogenesis. Appreciating factors that underlie the susceptibility of prematurely born infants to NEC is important for the development of new strategies aimed at the prevention and treatment of disease. In this review, we discuss defense mechanisms in the intestine and discuss how these systems may be insufficient in the prematurely born infant and thereby further contribute to initiation of NEC. In addition, based on a review of the literature, we suggest that, although numerous bacterial and viral pathogens have been associated with NEC, no individual organism is known to be responsible for disease. Finally, we comment on the possible role for probiotics in promoting maturation of intestinal defense mechanisms thereby attenuating or preventing the sequence of events that lead to NEC. (Pediatr Res 63: 117-123, 2008)

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“…Histopathology sections of intestine from infants with NEC reveal evidence of necrosis and inflammation (17,18). Neutrophils in particular seem to have a central role in the intestinal injury, and it has been shown that neutrophil depletion by vinblastine eliminated intestinal injury in a rat model of NEC (19).…”

mentioning

confidence: 99%

Modulation of Human Intestinal Epithelial Cell IL-8 Secretion by Human Milk Factors

2003

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Experimental necrotizing enterocolitis: The role of polymorphonuclear neutrophils

Cited by 42 publications

References 6 publications

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

Understanding the Susceptibility of the Premature Infant to Necrotizing Enterocolitis (NEC)

Modulation of Human Intestinal Epithelial Cell IL-8 Secretion by Human Milk Factors

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