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At least 19 recordsLinked to original sources
PubMed1993

Do infiltrating neutrophils contribute to the pathogenesis of indomethacin induced ulceration of the rat gastric antrum?

The potential involvement of neutrophils in the pathogenesis of indomethacin induced ulceration of the gastric antrum in the re-fed rat was studied. Indomethacin was associated with a time dependent increase in the extent and severity of ulceration, blood neutrophilia, neutrophil infiltration into the gastric antrum, and calcium ionophore induced immunoreactive leukotriene B4 (LTB4) release from the antrum ex vivo. Neutrophil infiltration into the antrum was detectable 1 hour after dosing with indomethacin, at which time damage was apparent microscopically but not macroscopically. Thus, cell infiltration may contribute to the development, if not the initiation, of ulceration. Consistent with this suggestion, oral dexamethasone (5 mg/kg) significantly attenuated indomethacin induced ulceration, the associated neutrophil infiltration, and calcium ionophore induced immunoreactive leukotriene B4 release from the gastric antrum and whole blood ex vivo, although the blood neutrophilia was unaffected. These results suggest that indomethacin induced ulceration of the rat gastric antrum may have a dependence on neutrophil infiltration for its pathogenesis.

Animals↗
PubMed2006

CXCL1/KC and CXCL5/LIX are selectively produced by corneal fibroblasts and mediate neutrophil infiltration to the corneal stroma in LPS keratitis.

The severity of corneal inflammation depends on the activity of infiltrating neutrophils responding to chemotactic factors such as CXC chemokines. This study examines the relative contribution of CXCL1/keratinocyte-derived chemokine (KC), CXCL2/monocyte-inhibitory protein-2 (MIP-2), and CXCL5/LPS-induced chemokine (LIX) in neutrophil recruitment to the corneal stroma during LPS keratitis, where neutrophils infiltrate the corneal stroma at 6 h after LPS injection and peak at 24 h. Consistent with this timeframe, KC was detected after 3 h, reached peak levels at 24 h, and decreased thereafter. In contrast, LIX production was not detected until 8 h after injection and peaked at 24 h. MIP-2 was detected at 3 h but did not reach the levels of KC and LIX. Cell types associated with corneal inflammation produced markedly different chemokines in vitro: Murine corneal fibroblasts (MK/T-1) produced LIX and KC in response to LPS but did not produce MIP-2, whereas peritoneal macrophages and neutrophils produced MIP-2 and KC but did not produce LIX. To determine the role of these chemokines in neutrophil recruitment to the cornea, anti-LIX, anti-KC, or anti-MIP-2 was injected into the corneal stroma of enhanced GFP chimeric mice prior to LPS, and total cell and neutrophil infiltration was examined. Antibody to LIX and KC, injected individually or in combination, significantly inhibited neutrophil recruitment to the cornea, whereas anti-MIP-2 had no inhibitory effect. Together, these findings demonstrate cell-specific production of CXC chemokines and show that LIX and KC mediate neutrophil recruitment into the cornea during LPS keratitis.

Animals↗
PubMed2001

Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma.

We evaluated the role of the tumor environment in the regulation of apoptosis of tumor-infiltrating neutrophils, the number of which correlates negatively with outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We examined three different parameters of apoptosis, namely morphological aspect, annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF) supernatants from patients with BAC significantly inhibited the 24-hour spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to BALF supernatants from control patients (64 +/- 4% versus 90 +/- 2% measured by annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in the patient's BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63% inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8, IL-6, IL-1beta and tumor necrosis factor-alpha had no significant effect. In an attempt to identify the cell origin of anti-apoptotic cytokines, we tested in vitro the effect of BAC cells (A549 cell line and primary culture derived from a patient's BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast, cell-free supernatants from tumor cells previously exposed to conditioned media from peripheral blood mononuclear cells and alveolar macrophages significantly inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted when conditioned media from mononuclear cells were previously treated with Abs against IL-1beta and tumor necrosis factor-alpha. As in vivo, neutralizing Abs against GM-CSF significantly inhibited the anti-apoptotic activity of cell culture supernatants, and combination with Abs against G-CSF had an additive effect. In vivo, GM-CSF and G-CSF were strongly expressed by tumor cells and moderately or not expressed by the normal epithelium, as assessed by immunohistochemical studies. These findings demonstrate that the tumor environment generates local conditions that prolong alveolar neutrophil survival through the production of soluble factors, thereby contributing to the persistence of the neutrophil alveolitis observed in BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1991

The role of leukotriene B4 in neutrophil infiltration in experimentally-induced inflammation of rat tooth pulp.

Inflammation was induced in rat dental pulp by applying bacterial lipopolysaccharide (LPS). Extirpated tissue samples from inflamed pulps were incubated in vitro in a Krebs buffer containing Ca2+ ionophore A23187, and leukotriene (LT) B4 released into the medium was determined by radio-immunoassay. Production of LTB4 could be detected three to 24 h after the application of LPS and showed a maximum at 12 h. Histologically, marked infiltration of neutrophils, but not other leukocytes, was characteristically observed in the LPS-applied pulps, and the temporal change in neutrophil infiltration was almost parallel, but somewhat more delayed than LTB4 production. When BW755C, a dual inhibitor of cyclo-oxygenase and lipoxygenase, was given to the animals before the application of LPS, both the production of LTB4 and the number of infiltrated neutrophils were significantly decreased, whereas administration of indomethacin had no effect. These results suggest that LTB4 may be involved in neutrophil infiltration in pulpal inflammation. It was also suggested that a major early source of LTB4 in experimental pulpitis was leukocytes, primary neutrophils, because the synthesis of LTB4 in the inflammed pulp was diminished by depletion of circulating leukocytes with cyclophosphamide prior to the application of LPS.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed2003

Honokiol protects rat brain from focal cerebral ischemia-reperfusion injury by inhibiting neutrophil infiltration and reactive oxygen species production.

We have previously shown that honokiol, an active component of Magnolia officinalis, displayed protective effect against focal cerebral ischemia-reperfusion (FCI/R) injury in rats. Production of reactive oxygen species (ROS) and infiltration of neutrophils to injured tissue play deleterious roles during cerebral ischemia. To study the mechanism(s) in mediating neuroprotective effect of honokiol, FCI/R-induced neutrophil infiltration and lipid peroxidation in brain tissue, and activation of neutrophils in-vitro were examined. Intravenous administration of honokiol (0.01-1.0 microg/kg) 15 min before (pretreatment) or 60 min after (post-treatment) middle cerebral artery occlusion reduced the total infarcted volume by 20-70% in dose-dependent manner. Pretreatment or post-treatment of honokiol at concentration of 0.1 and 1.0 microg/kg significantly decreased the neutrophil infiltration in the infarcted brain. Time course of neutrophil infiltration was performed in parallel with the lipid peroxidation in infracted brain tissue during FCI/R injury. The results indicate that honokiol can protect brain tissue against lipid peroxidation and neutrophil infiltration during FCI/R injury and cerebral infarction induced by FCI/R is accompanied with a prominent neutrophil infiltration to the infarcted area during FCI/R course. In-vitro, honokiol (0.1-10 microM) significantly diminished fMLP (N-formyl-methionyl-leucyl-phenylalanine)- or PMA (phorbol-12-myristate-13-acetate)-induced neutrophil firm adhesion, a prerequisite step behind neutrophil infiltration, and ROS production in neutrophils. Intracellular calcium overloading activates calcium-stimulated enzymes and further exaggerates FCI/R injury. Honokiol (0.1-10 microM) impeded the calcium influx induced by fMLP (a receptor agonist), AlF(4)(-) (a G-protein activator) or thapsigargin (an intracellular calcium pool releaser). Therefore, we conclude that the amelioration of FCI/R injury by honokiol can be attributed to its anti-oxidative and anti-inflammatory actions through, at least in part, limiting lipid peroxidation and reducing neutrophil activation/infiltration by interfering firm adhesion, ROS production, and calcium overloading that may be primed/activated during FCI/R injury.

Animals↗
PubMed1999

Neutrophil infiltration into human gliomas.

Human gliomas were analysed for the infiltration of neutrophils using immunohistochemistry by staining sections for CD15-positive and myeloperoxidase-positive cells. Over 70% of all glioma samples analysed (n = 105) had significant neutrophil infiltration, but there was a marked and significant correlation between tumour grade and the extent of the neutrophil infiltration. In the low grade tumours only 40-50% had significant infiltration, while in glioblastoma multiforme over 85% of the samples analysed had significant infiltration. Numbers of neutrophils infiltrating glioblastoma multiforme tumours were also greater than in the other tumour groups. Circulating white blood cell counts were elevated above the normal range in all glioma patients, but this elevation was entirely due to increased numbers of circulating neutrophils. Again, the highest numbers of circulating neutrophils were seen in the glioblastoma multiforme patients. These experiments indicate that glioma-derived factors may directly or indirectly affect the number of circulating neutrophils and influence their infiltration into the tumours.

Bone Marrow↗
PubMed2004

Involvement of MIP-2 and CXCR2 in neutrophil infiltration following injection of late apoptotic cells into the peritoneal cavity.

Apoptotic cells are cleared by phagocytes, such as macrophages, as soon as they appear in vivo. If apoptosis occurs acutely, however, macrophages may be outnumbered by apoptotic cells, which causes late apoptosis. We previously showed that injection of late apoptotic cells into the peritoneal cavity led to transient infiltration of neutrophils. In this study, we examined the involvement of MIP-2 and CXCR2 in the neutrophil infiltration. We first produced a recombinant MIP-2 protein, and a fusion protein between CXCR2 and GST in E. coli, and then generated anti-MIP-2 antibodies and anti-CXCR2 antibodies in rabbits. We then confirmed their specificity by Western blotting analysis and flow cytometry. Injection of late apoptotic cells, such as P388 cells treated with etoposide for 24 hours and CTLL-2 cells cultured in IL-2-free medium for 28 hours, induced neutrophil infiltration into the peritoneal cavity, as expected. The antibodies, but not control antibodies against GST, suppressed the neutrophil infiltration to the level caused by injection of normal (viable) cells, suggesting that MIP-2 and CXCR2 are mainly involved in the neutrophil infiltration caused by late apoptotic cells.

Animals↗
PubMed1983

Subcutaneous neutrophilic infiltrates in acute febrile neutrophilic dermatosis.

A patient had an evolving hematologic disorder, accompanied by tender, red, subcutaneous nodules. Histologically, there were dense neutrophilic infiltrates confined to the subcutaneous adipose tissue. Three months later, a typical episode of acute febrile neutrophilic dermatosis (ND) developed in the patient, and she was found to have acute myeloid leukemia. In addition to the dermis, the neutrophilic infiltrates of ND occasionally involve the subcutis. As seen in our patient, the infiltrates are rarely limited to the subcutaneous tissue.

Acute Disease↗
PubMed2005

Invasive micropapillary carcinomas of the ampullo-pancreatobiliary region and their association with tumor-infiltrating neutrophils.

Invasive micropapillary carcinoma, originally described as a distinctive type of invasive carcinoma in the breast, is being increasingly recognized as a separate entity in many other organs; however, it has not yet been documented in the pancreas or periampullary region. In this study, 313 pancreatic and 73 periampullary carcinomas were reviewed to investigate the micropapillary pattern in this location. Eight periampullary and eight pancreatic cases (4%) were composed at least focally (>20%) of invasive micropapillary carcinoma. The patients were 10 males and six females, mean age 69 years. The mean tumor size was 3.2 cm. Lymph node metastasis was detected in 11/15 cases. The median survival was 8 months (all were resected). Invasive micropapillary carcinoma was characterized by small, closely packed micropapillary clusters (without fibrovascular cores) lying within clefts. The cells had moderate degree of nuclear atypia. In nine cases, there was abundant inflammation composed of neutrophils concentrating around the tumor cells, both intraepithelial ('cannibalism') and stromal. Molecules implicated in abnormalities of tumor cell-stroma adhesion, galectin-3 and E-cadherin were expressed in the cytoplasm of 11/11 and 9/11 cases, respectively. Reversal of cell polarity was observed by MUC 1 in all 11 cases tested, which showed labeling in the stroma-facing surfaces of the micropapillary clusters, also confirming that the clefts are not merely a processing artifact, but indeed a true biologic alteration. In conclusion, invasive micropapillary carcinoma constitutes 4% of carcinomas in the pancreatic/periampullary region and is commonly associated with abundant neutrophilic infiltrates. Invasive miropapillary carcinoma appears to be more common in periampullary than in pancreatic invasive micropapillary carcinoma would qualify as poorly differentiated both based on pattern and the median survival (8 months)..

Adult↗
PubMed2003

Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death.

Increased numbers of tumor-infiltrating neutrophils are linked to poorer outcome in patients with adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype. Hepatocyte growth factor (HGF) is a pleiotropic cytokine operating through activation of the proto-oncogene c-met and is a factor of poor prognosis in various cancers. Reports that neutrophils produce HGF led us to investigate their participation in the aerogenous spread of tumor cells and the prognosis of BAC, through the effect of HGF on c-met-expressing tumor cells. Immunoreactive HGF was detected in bronchoalveolar lavage fluid (BALF) supernatants from 34 of 36 patients, whereas it was undetectable in BALF from healthy controls. The HGF thus detected was locally produced, because HGF mRNA was expressed by the patients' fresh alveolar cells, and HGF protein was detected in 24-h culture supernatants. In immunocytochemical studies of BALF cytospin preparations and tumor specimens from the patients, neutrophils were always HGF-positive, whereas alveolar macrophages and tumor cells gave inconsistent results. Alveolar neutrophil-derived HGFs induced significant, concentration-dependent migration of BAC-derived tumor cells in vitro, and this effect was inhibited by anti-HGF neutralizing antibodies. Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha (present in the lung tumor microenvironment) provoked HGF release from neutrophil intracellular stocks, and the capacity of blood neutrophils from BAC patients to produce HGF was unaltered. Immunochemical studies of c-met expression in BALF cytospin preparations and tumor sections showed that most HGF receptor-bearing cells were tumor cells. High HGF levels in BALF supernatants were significantly associated with poorer outcome in patients with BAC and were an independent predictor of clinical outcome in multivariate analysis. Altogether, our results support the notion that BAC generates a local environment that attracts functionally normal neutrophils from peripheral blood and leads to neutrophil release of biologically active HGF on contact with HGF receptor-expressing tumor cells, thereby contributing to poorer patient outcome.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2003

Interferon-beta prevents cytokine-induced neutrophil infiltration and attenuates blood-brain barrier disruption.

Inflammation can contribute to brain injury, such as that resulting from ischemia or trauma. The authors have previously shown that the cytokine interferon-beta (IFN-beta) affords protection against ischemic brain injury, which was associated with a diminished infiltration of neutrophils and a reduction in blood-brain barrier (BBB) disruption. The goal of the current study was to directly assess the effects of IFN-beta on neutrophil infiltration, with the use of an in vivo assay of neutrophil infiltration with relevance to ischemic brain injury. Intrastriatal injection of recombinant rat cytokine-induced neutrophil chemoattractant-1, a member of the interleukin-8 family (1 microg in 1 microl), triggered massive infiltration of neutrophils and extensive BBB disruption 6 hours later, as measured using immunofluorescence microscopy and magnetic resonance imaging in the rat, respectively. Depleting the animals of neutrophils before interleukin-8 injection prevented BBB disruption. Treatment with IFN-beta (5 x 106 U/kg) almost completely prevented neutrophil infiltration and attenuated BBB damage. Gelatinase zymography showed matrix metalloproteinase-9 expression in the ipsilateral striatum after interleukin-8 injection. Both neutrophil depletion and IFN-beta treatment downregulated matrix metalloproteinase-9. IFN-beta has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN-beta as a treatment that can attenuate acute brain inflammation is considered.

Animals↗
PubMed2005

Intranasal inoculation of Chlamydia trachomatis mouse pneumonitis agent induces significant neutrophil infiltration which is not efficient in controlling the infection in mice.

Previous studies have shown that chlamydial infection is accompanied by significant infiltration of neutrophils at the site of infection. However, the role of neutrophils in host defence against chlamydial infection is not clearly understood. Using genetically different inbred mouse strains and CXCR-2 gene knockout (KO) mice, we examined the mechanism for neutrophil recruitment and the role of neutrophils during chlamydial lung infection. Our data showed that C3H mice exhibited significantly higher and more persistent neutrophil infiltration in the lung than did C57BL/6 mice following Chlamydia trachomatis mouse pneumonitis infection. The massive neutrophil infiltration in C3H mice was paralleled by high-level expression of CXCR-2 and its ligands, CXC chemokines (macrophage inflammatory protein 2, cytokine-induced neutrophil attractant (KC) and lipopolysaccharide-induced CXC chemokine), and proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-1 and interleukin-6) in the lung. Although much greater infiltration of neutrophils was observed in C3H mice than in C57BL/6 mice, the former mice had more severe disease and higher in vivo chlamydial growth than the latter. Moreover, CXCR-2 KO mice, which revealed a dramatic reduction in neutrophil activity, showed comparable chlamydial infection to wild-type mice. These results suggest that neutrophils are not efficient for controlling chlamydial lung infection.

Administration, Intranasal↗
PubMed2006

Neutrophil infiltration and chemokines.

Neutrophil infiltration is mainly mediated by ELR+ CXC chemokines and is regulated through interactions between various stimulants and cells, which are perhaps more complex than previously thought. In this review, I describe the current view of the roles of neutrophil-selective chemokines such as IL-8, MIP-2, and KC by choosing several in vivo models. I also illustrate how these three chemokines are induced and how they are involved in neutrophil infiltration. Finally, I introduce synthetic compounds with high efficacy in the prevention of ischemia reperfusion injury.

Animals↗
PubMed2004

Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury.

The release of reactive oxygen species (ROS) by neutrophils, which infiltrate the region of damage following spinal cord injury (SCI), was investigated to determine if such release is significant following spinal cord injury. The relationship of extracellular levels of hydroxyl radicals and hydrogen peroxide obtained by microdialysis sampling and oxidized protein levels in tissue to neutrophil infiltration following spinal cord injury was examined. Neither of the reactive oxygen species were elevated in the site of spinal cord injury relative to their concentrations in normal tissue at a time (24 h) when the numbers of neutrophils were maximum in the site of injury. Surprisingly, ablation with a neutrophil antiserum actually increased the level of oxidized proteins in Western blots. Thus, our findings are (1) that neutrophils, which infiltrate the site of damage following a spinal cord injury, do not release detectable quantities of reactive oxygen species; and (2) that the presence of neutrophils reduces the concentrations of oxidized proteins in the site of spinal cord injury. Therefore, release of reactive oxygen species by neutrophils does not contribute significantly to secondary damage following spinal cord injury. Reduced levels of oxidized proteins in the presence of neutrophils may reflect removal of damaged tissue by neutrophils.

Animals↗
PubMed2000

Elafin is induced in epidermis in skin disorders with dermal neutrophilic infiltration: interleukin-1 beta and tumour necrosis factor-alpha stimulate its secretion in vitro.

BACKGROUND: Elafin, an elastase inhibitor produced by keratinocytes, is overexpressed in the subcorneal region of skin affected by psoriasis, a major feature of which is epidermal infiltration by neutrophil leucocytes. OBJECTIVES: We studied the expression of elafin in the epidermis in other skin disorders characterized by dermal neutrophil infiltration and in skin disorders with dermal lymphocyte infiltration. PATIENTS/METHODS: We examined biopsies from the lesional skin of patients with Behçet's syndrome, Sweet's syndrome, pyoderma gangrenosum, cutaneous allergic vasculitis and acute bacterial infection (cellulitis), and from the skin of patients with chronic prurigo, discoid lupus erythematosus and psoriasis. We performed in vitro experiments using cultured keratinocytes treated with mediators such as interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha, IL-6, neutrophil elastase and interferon (IFN)-gamma. RESULTS: Anti-elafin antibody showed a strong reaction with the subcorneal region of the epidermis in patients with Behçet's syndrome, Sweet's syndrome, pyoderma gangrenosum, cutaneous allergic vasculitis and acute bacterial infection (cellulitis), but showed no reaction in skin from patients with dermal lymphocyte infiltration such as is seen in chronic prurigo and discoid lupus erythematosus. The in vitro experiments demonstrated that treatment with IL-1 beta and TNF-alpha resulted in 2.6-fold and 4-fold stimulation of elafin secretion, respectively, whereas IL-6, neutrophil elastase and IFN-gamma caused no significant changes in elafin release. CONCLUSIONS: These results suggest that inflammatory mediators such as IL-1 beta or TNF-alpha secreted by dermal neutrophils may be involved in overexpression of elafin in keratinocytes; this could protect the epidermis from degradation by dermal neutrophil infiltration.

Cell Culture Techniques↗
PubMed1992

Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats.

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammatory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4 micrograms/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutrophil infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37 degrees C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact rats. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.

Animals↗
PubMed1996

Oxygen free radical content and neutrophil infiltration are important determinants in mucosal injury after rat small bowel transplantation.

Mucosal injury is an immediate event following revascularization of small intestinal grafts in the context of transplantation (SBTx). The generation of oxygen free radicals (OFR) and tissue infiltration by activated neutrophils are consequences of ischemia and reperfusion and known causative factors of tissue injury; to delineate their role in the reperfusion injury occurring after cold preservation of the intestine and subsequent transplantation was the aim of this study. Prior to orthotopic SBTx in Sprague-Dawley rats, grafts were stored in cold (4 degrees C) Ringer's lactate solution for 1 (n=6), 2 (n=7), and 4 hr (n=7). Small bowel biopsy specimens were obtained before harvesting, at the end of the (cold) ischemic period and immediately before unclamping (i.e., before revascularization) and 30, 60, 120 min, and 24 hr after transplantation to evaluate tissue injury by histology, OFR production, (measured by luminol-enhanced chemiluminescence [LCL]), and the degree of neutrophil infiltration by myeloperoxidase staining. Reperfusion of the graft significantly worsened the histologically graded mucosal injury compared with that seen before unclamping. However, 24 hr after engraftment, mucosal morphology was restored almost completely. OFR production increased significantly during the early phases of reperfusion (30, 60, and 120 min) and returned to control values after 24 hr. Reperfusion of the graft was associated with a marked increase in the number of mucosal neutrophils. The present study indicates that OFR production and neutrophilic infiltration commence and progressively increase with graft reperfusion. These changes parallel the mucosal injury. Ischemic intervals of 4 hr were not associated with a statistically significant greater ischemic-injury patterns compared with 1- and 2-hr intervals. The profound changes associated with reperfusion probably overshadow the minor, yet likely, progressive injury patterns associated with longer ischemia times.

Animals↗