摘要:

Porifera (sponge) form the lowest metazoan phylum and share a common ancestor with other metazoan phyla. In the present study, it is reported that sponges possess molecules that are similar in structure to those molecules involved in the immune system in mammals. Experiments with the marine spongesGeodia cydoniumandSuberites domunculahave been performed on tissue (auto- and allografting) as well as on a cellular level. The studies revealed that sponges are provided with elements of the mammalian innate immune system, such as molecules containing scavenger receptor cysteine-rich domains. Furthermore, macrophage-derived cytokine-like molecules have been identified that are up-regulated during the grafting process. In addition, the (2′-5′)oligoadenylate synthetase system exists in sponges. "Precursors" of the second type of immune response in mammals, the adaptive immune system, have been traced in sponges. It is shown that the expression of a lymphocyte-derived cytokine from mammals is up-regulated during non-self-recognition inS. domuncula.Finally, inG. cydonium,two classes of receptors that comprise Ig-like domains have been identified: the receptor tyrosine kinases and the non-enzymic sponge adhesion molecules. They contain two polymorphic Ig-like domains that are grouped to the variable set of immunoglobulins. The expression of these molecules is also up-regulated during the grafting process. It is concluded that sponges are already provided with a series of elements used in higher vertebrates for both the innate and the adaptive immune recognition.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.We hypothesized that endothelin-A (ET-A) receptor activation plays a central role in intestinal ischemia-reperfusion-induced hemodynamic changes and may trigger the process of mucosal barrier destruction. Our aims were to investigate and compare the effects of systemic and intragraft ET-A receptor antagonist therapy during the early revascularization phase of small bowel transplants.Methods.In Groups 1, 2, and 3 orthotopic small bowel autotransplants were performed in anesthetized dogs. Group 4 served as sham-operated control. Group 2 was treated i.v. with the ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. In Group 3, intragraft infusion of the ETR-p1/fl peptide was applied during cold ischemia. The mucosal myeloperoxidase activity and the free radical-producing capacity of the granulocytes passing the intestinal graft were determined, and the systemic hemodynamic features were recorded. The extent of the mucosal injury was determined from tissue biopsies taken after 4 hr of reperfusion.Results.Reperfusion progressively decreased the mesenteric blood flow, increased the mesenteric vascular resistance, and enhanced the accumulation and free radical production capacity of the leukocytes. These changes were significantly inhibited in Group 2 with systemic (i.v.) administration of the ET-A receptor antagonist. The local, intragraft treatment improved the mesenteric hemodynamic changes and decreased the accumulation but not the activation of the circulating leukocytes. The structural injury of the graft was prevented in both treated groups.Conclusions.Endothelins are involved in the hemodynamic events leading to structural injury of the intestinal graft after ischemia-reperfusion. The antagonism of intestinal ET-A receptors by a combination of local and systemic drug delivery offers a rational treatment modality in these conditions.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Attempts to attenuate lung reperfusion injury by administration of inhaled nitric oxide have yielded conflicting results. We hypothesized that the inspired oxygen fraction may play an important role in determining the outcome of nitric oxide therapy.Methods.Rat lungs were reperfused in a circuit incorporating a support animal either immediately after flushing (group A) or after 24-hr hypothermic storage (groups B-D). During the first 10 min of reperfusion, grafts were ventilated with 95% oxygen in groups A and B, 95% oxygen and 20 ppm nitric oxide in group C, and 20% oxygen and 20 ppm nitric oxide in group D. Ventilation during the subsequent 50 min of reperfusion was with 100% oxygen only, in all groups.Results.Graft function in group B was poor compared to group A in terms of blood flow and pulmonary artery and peak airway pressures. In group C, although 5 out of 10 grafts functioned at control levels, the remainder performed poorly. Function in group D, on the other hand, was uniformly good.Conclusions.Inhaled nitric oxide can prevent lung reperfusion injury, but this effect may be compromised by concurrent ventilation with high oxygen concentrations.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Pathophysiological states that produce intestinal ischemia/reperfusion injury (I/R) initiate an inflammatory cascade and cause ileus. The aims of this study were to investigate the local cellular responses and molecular mechanisms, which contribute to intestinal dysmotility after selective intestinal I/R injury.Methods.ACI rats were subjected to 75 min SMA clamp-induced ischemia followed by reperfusion and were killed at 0 min, 30 min, and 24 hr. Whole mounts of the jejunum were used to immunohistochemically quantify alterations in leukocytes, and circular muscle strips were used to assess organ bath muscle function. Muscularis and mucosa extracts were isolated from the intestine and used for reverse transcription assisted polymerase chain reaction mRNA measurements of granulocyte-colony stimulating factor and interleukin-6, and for determination of nuclear factor kappa B and Stat3 activation.Results.Intestinal I/R injury resulted in the significant recruitment of neutrophils and monocytes into the intestinal muscularis and a functional suppression in jejunal circular muscle contractions. These I/R injury induced cellular responses were preceded by the molecular activation of nuclear factor kappa B, upregulation of granulocyte colony-stimulating factor and interleukin-6 mRNA and phosphorylation of the downstream signaling and transcription factor Stat3.Conclusions.I/R injury evokes a molecular and cellular inflammatory response within the intestinal muscularis that is associated with a subsequent decrease in intestinal motility.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.The maturation of dendritic cells (DC) is influenced by various factors, in particular cytokine-mediated signaling events. These include modulation of the activation of nuclear factor kappa B (NF-κB), which controls the transcription of genes encoding major histocompatibility complex (MHC) antigens, and costimulatory/accessory molecules for T-cell activation. Here, we investigated the influence of cyclosporine A (CsA) on the in vitro maturation of DC, and on the nuclear translocation and DNA binding of NF-κB.Methods.DC progenitors were propagated from mouse bone marrow in granulocyte-macrophage colony-stimulating factor (GM-CSF) or in GM-CSF plus either transforming growth factor (TGF)-β or interleukin (IL)-4, in the presence or absence of CsA (1 μg/ml). After 5 days of culture, cell surface expression of MHC class I/II, CD40, CD80, and CD86 was analyzed by flow cytometry, and nuclear NF-κB proteins by electrophoretic mobility shift, antibody supershift, and Western blot assays. The antigen-presenting function of DC was determined in one-way mixed leukocyte reactions.Results.Exposure of replicating DC progenitors propagated in GM-CSF or GM-CSF+TGF-β to CsA reduced costimulatory molecule expression, without affecting MHC antigen expression. Nuclear extracts from the CsA-treated DC revealed a decrease in nuclear translocation of NF-κB (p50). Mixed leukocyte reaction data were consistent with the flow cytometry and gel shift assay results, and showed reduced allostimulatory ability of the CsA-treated cells compared with untreated controls. Addition of IL-4 from the start of DC cultures conferred resistance to CsA-induced inhibition of NF-κB nuclear translocation and DC maturation.Conclusions.CsA differentially inhibits the expression of key cell surface costimulatory molecules by in vitro-generated DC. This effect can be overcome, at least in part, by IL-4 and augmented by TGF-β. The inhibition is linked to a decrease in nuclear translocation/DNA binding of NF-κB. Thus, CsA can alter the antigen-presenting function of DC for T-cell activation.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Upon exposure to cytokines, endothelial cells may undergo profound alterations of vasomotor function. In this study, we characterized the relation-ship between coronary epicardial and microvascular vasomotor function and expression of specific cytokine patterns in human heart transplant recipients.Methods.We studied 49 cardiac transplant recipients, without acute rejection or infection at an average of 6±3 months after transplantation. Coronary resistance vessel function was measured in an endothelium-dependent manner with acetylcholine (5 and 150 μg/5 min; intracoronary injection) and in an endothelium-independent manner with adenosine (400 and 800 μg/5 min; intracoronary injection) using an intracoronary Doppler flow wire. Simultaneous epicardial diameter changes were measured using quantitative coronary angiography. Coronary sinus and aortic serum levels of soluble interleukin (IL)-2 receptor and soluble tumor necrosis factor-α receptors (sTNF-R1 and sTNF-R2), TNF-α, and IL-6 were determined. Transcardiac cytokine release (coronary sinus minus aortic levels) was correlated with coronary vasomotor function.Results.The highest amounts of cardiac cytokine release were observed for IL-6 (32±14% increase) and sTNF-R1 (26±13% increase). A significant inverse correlation between microvascular endothelial function and cardiac release of soluble IL-2 receptor (P=0.04) and IL-6 (P=0.03) was detected, whereas a positive correlation was observed to sTNF-R1 (P=0.004). Distal epicardial endothelial vasomotion was inversely correlated to transcardiac sTNF-R2 release (P=0.03).Conclusions.Cytokine production and activation, a common phenomenon early after heart transplantation, is related at least in part to endothelial vasomotor dysfunction of the epicardial and microvascular compartment. These results support the hypothesis that coronary endothelial dysfunction after cardiac transplantation is an immunologic phenomenon. Since endothelial dysfunction seems to be a crucial step in the pathogenesis of cardiac allograft vasculopathy, coronary cytokine suppression should be a therapeutic target of improved future immunosuppressive regimens.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Tuberculosis is an important cause of morbidity and mortality in renal transplant recipients, but there are insufficient data regarding the efficacy and complications of therapy and of INH prophylaxis.Methods.This study is a retrospective review of the records of 880 renal transplant recipients in two centers in Turkey.Results.Tuberculosis developed in 36 patients (4.1%) at posttransplant 3-111 months, of which 28 were successfully treated. Eight patients (22.2%) died of tuberculosis or complications of anti-tuberculosis therapy. Use of rifampin necessitated a mean of 2-fold increase in the cyclosporine dose, but no allograft rejection occurred due to inadequate cyclosporine levels. Hepatotoxicity developed in eight patients during treatment, two of whom died due to hepatic failure. No risk factor, including age, gender, renal dysfunction, hepatitis C, or past hepatitis B infection, was found to be associated with development of hepatic toxicity. A subgroup of 36 patients with a past history of or radiographic findings suggesting inactive tuberculosis, was considered to be at high risk for developing active disease, of whom 23 were given isoniazid (INH) prophylaxis. None versus 1 of 13 (7.7%) of cases with and without INH prophylaxis, respectively, developed active disease (P>0.05). None of the patients receiving INH had hepatic toxicity or needed modification of cyclosporine dose.Conclusions.These data show that tuberculosis has a high prevalence in transplant recipients, that it can effectively be treated using rifampin-containing anti-tuberculosis drugs with a close follow-up of serum cyclosporine levels, and that INH prophylaxis is safe but more experience is needed to define the target population.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Cytomegalovirus (CMV) resistance to ganciclovir has become increasingly common in acquired immu;nodeficiency syndrome patients but has only rarely been reported in recipients of solid organ transplants.Methods.A retrospective study of ganciclovir susceptibility testing of CMV isolates recovered from lung transplant recipients was performed. Patients with CMV isolates having partial (1<IC50<3 μg/ml) or full resistance (IC50≥3 μg/ml) to ganciclovir determined by plaque reduction assay were included in a case-control study to identify risk factors for ganciclovir resistance.Results.Between 2/91 and 5/98, 18 patients (5.2% of patients transplanted) were found to have CMV infections with some degree of ganciclovir resistance (4 partially, 14 fully resistant). More positive viral blood cultures (3.2±2.5 vs. 1.6±1.4 CMV positive cultures,P=0.02) and more episodes of CMV pneumonitis (0.24±0.23 vs. 0.10±0.17 episodes/bronchoscopy,P=0.02) occurring before the detection of resistance were seen among resistant patients than controls. Ganciclovir-resistant patients received more antithymocyte globulin during induction (70±44 vs. 45±39 mg/kg,P=0.03) and received ganciclovir for a greater number of days (79±52 vs. 64±53 days,P=0.005) before the detection of resistance than controls. Ganciclovir-resistant patients had a shorter survival and an earlier onset of bronchiolitis obliterans syndrome compared with patients in the transplant database at Washington University.Conclusions.Ganciclovir-resistant CMV infection is a serious complication of solid organ transplantation associated with more episodes of viremia, more frequent disease, earlier onset of bronchiolitis obliterans and shorter survival. The use of antithymocyte globulin and prolonged exposure to ganciclovir are risk factors for the development of ganciclovir resistance.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID