Biomedical subjects

Z Song

Publications and source records attributed to Z Song.

At least 19 recordsLinked to original sources

PubMed2006

Rapid eye movement sleep deprivation selectively impairs recall of fear extinction in hippocampus-independent tasks in rats.

Previous studies have shown that rapid eye movement (REM) sleep deprivation (RSD) exerts a detrimental effect on some memory tasks. However, whether post-learning RSD impairs memory for fear extinction, an important model of inhibitory learning, remains to be elucidated. The present study examined the effects of post-extinction RSD from 0 to 6 h and 6 to 12 h on recall of fear extinction tested 24 h after extinction training. We found that RSD from 0 to 6 h significantly increased freezing when recall of extinction of cued fear was tested in the context in which rats received extinction training whereas RSD from 6 to 12 h had no effect (experiments 1 and 2, two hippocampus-independent memory tasks). RSD at either time point had no effect on freezing when recall of extinction of cued fear was tested in the context different from that in which extinction training occurred (experiment 3, a hippocampus-dependent memory task). Additionally, we observed no effect of RSD at either time point on freezing during recall test for extinction of contextual fear (experiment 4, a hippocampus-dependent memory task). These results suggest that the effects of post-extinction RSD on memory for fear extinction are complex. RSD impairs recall of fear extinction in hippocampus-independent tasks, but does not affect recall of fear extinction in hippocampus-dependent tasks. Our findings extend previous research on the effects of RSD on learning and memory and support the notion that REM sleep is involved in memory process of certain tasks.

Acoustic Stimulation↗

PubMed2006

Heavy metal contamination and distribution in the urban environment of Guangzhou, SE China.

Ever-increasing heavy metal accumulation in the urban environment of Guangzhou, the largest light industrial production base and one of the most rapidly developing cities in China, poses a serious threat to environment as well as to human health in the region. As a sink or source, urban deposits are good indicators of the level and extent of heavy metal accumulation in the surface environment. The aim of this preliminary study was to examine the distribution of heavy metal contamination in the urban environment of Guangzhou. It was based on a systematic sampling of road dusts and corresponding gully sediments along major roads running mainly through commercial and residential to industrial districts of the city. In addition to road dusts and gully sediments, ceiling dusts from the Pearl River Tunnel were also collected to characterize anthropogenic emissions dominated by traffic-related activities. In general, the level of Cd, Cu, Pb and Zn contaminations were more severe on the industrialized side of Guangzhou than on the western side where heavy traffic and industrial activities were limited. The primary determinants of the level of heavy metal contamination and the distribution of this contamination in the urban environment of Guangzhou were the site-specific conditions of its urban setting, particularly the types of industries, the nature of the traffic flow, sample residence times and variations in grain size of the particulate contaminants. This study highlights the complexity of the urban system and indicates that in just such a system individual urban components should be interlinked to assess the long-term environmental and health effects of heavy metal contamination. Among the heavy metals tested--Cd, Cu, Pb and Zn--the level of Zn contamination was the most severe and widespread, and thus requires immediate attention.

China↗

PubMed2006

Livin promotes Smac/DIABLO degradation by ubiquitin-proteasome pathway.

Livin, a member of the inhibitor of apoptosis protein (IAP) family, encodes a protein containing a single baculoviral IAP repeat (BIR) domain and a COOH-terminal RING finger domain. It has been reported that Livin directly interacts with caspase-3 and -7 in vitro and caspase-9 in vivo via its BIR domain and is negatively regulated by Smac/DIABLO. Nonetheless, the detailed mechanism underlying its antiapoptotic function has not yet been fully characterized. In this report, we provide, for the first time, the evidence that Livin can act as an E3 ubiquitin ligase for targeting the degradation of Smac/DIABLO. Both BIR domain and RING finger domain of Livin are required for this degradation in vitro and in vivo. We also demonstrate that Livin is an unstable protein with a half-life of less than 4 h in living cells. The RING domain of Livin promotes its auto-ubiquitination, whereas the BIR domain is likely to display degradation-inhibitory activity. Mutation in the Livin BIR domain greatly enhances its instability and nullifies its binding to Smac/DIABLO, resulting in a reduced antiapoptosis inhibition. Our findings provide a novel function of Livin: it exhibits E3 ubiquitin ligase activity to degrade the pivotal apoptotic regulator Smac/DIABLO through the ubiquitin-proteasome pathway.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Decay of Loschmidt echo enhanced by quantum criticality.

We study the transition of a quantum system from a pure state to a mixed one, which is induced by the quantum criticality of the surrounding system E coupled to it. To characterize this transition quantitatively, we carefully examine the behavior of the Loschmidt echo (LE) of E modeled as an Ising model in a transverse field, which behaves as a measuring apparatus in quantum measurement. It is found that the quantum critical behavior of E strongly affects its capability of enhancing the decay of LE: near the critical value of the transverse field entailing the happening of quantum phase transition, the off-diagonal elements of the reduced density matrix describing S vanish sharply.

Journal Article↗

PubMed2006

Suppression of tumor growth using a recombinant adenoviral vector carrying the dominant-negative mutant gene Survivin-D53A in a nude mice model.

Survivin (SVV), an inhibitor of apoptosis protein, is found to be upregulated in many cancers. We previously demonstrated that a dominant-negative mutant SVV-D53A was able to induce apoptosis in a p53-independent manner. Here, we report the construction and characterization of a recombinant replication-deficient adenoviral vector encoding a human SVV-D53A gene for its effectiveness against tumor growth both in vitro and in vivo. Transfection of liver tumor cells QGY-7703 with Ad-SVV-D53A results in significant apoptosis as measured by an increase in sub-G1 DNA content, procaspase-9 activation and further downstream PARP-1 cleavage. Furthermore, animal studies using QGY-7703 liver carcinoma xenografts in nude mice revealed that treatment of QGY-7703 cells with dominant-negative SVV-D53A, but not with wild-type SVV-adenovirus, prevents tumor outgrowth, inhibits growth of established tumors and results in a notably improved survival advantages in xenograft studies. Both the transferase-mediated dUTP nick-end labeling assay and immunostaining experiment demonstrated that tumor growth inhibition is associated with apoptosis induced by SVV-D53A expression. Taken together, these data suggest that recombinant adenovirus Ad-SVV-D53A carrying a Survivin dominant-negative gene SVV-D53A promotes apoptosis-mediated tumor suppression and could potentially be a promising candidate for cancer therapies.

Adenoviridae↗

PubMed2006

Site of ATP and phenylephrine synergistic stimulation of vasopressin release from the hypothalamo-neurohypophyseal system.

ATP and norepinephrine are neurotransmitters carrying cardiovascular information to vasopressin (AVP) neurones. As shown previously, exposure of hypothalamo-neurohypophyseal system explants to ATP and phenylephrine (PE) (alpha(1)-adrenergic agonist) causes a significantly larger increase in AVP release than with either agent alone and converts the response from a transient to a sustained stimulation of AVP release. Potential mechanisms for this synergism include presynaptic stimulation of excitatory afferent input (i.e. glutamate release), postsynaptic activation of receptors on AVP neurones, modulation of stimulus-secretion coupling in the neural lobe and/or involvement of glial/neuronal interactions. The response to ATP + PE (100 microM each) was not altered in the presence of either a cocktail of ionotropic glutamate receptor antagonists (CNQX + AP5) or a nonselective metabotropic glutamate receptor antagonist [(RS)-alpha-methyl-4-carboxyphenylglycine]. Thus, it is not dependent on activation of glutamate receptors. Treatment with tetrodotoxin (3 microM) eliminated the response to ATP + PE. Because this could reflect blockade of action potentials propagated from the AVP perikarya to the nerve terminals in the neural lobe or action potentials generated in the neural lobe directly, synergism in the neural lobe was addressed by perifusing isolated neural lobes with ATP and PE alone or together. Synergistic stimulation of AVP release by ATP + PE was not observed in isolated, perifused neural lobes. Thus, the synergistic effect persists in the absence of glutamate transmission, is not due to synergistic actions of P(2) and alpha(1)-adrenergic receptors occurring at the level of the neural lobe and requires action potentials in either the hypothalamus or neural lobe.

Adenosine Triphosphate↗

PubMed2005

Tumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in mice.

BACKGROUND: Collagen induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) amenable to immunotherapy directed against tumour necrosis factor alpha (TNFalpha). OBJECTIVE: To evaluate whether local TNF receptor (TNF-R) gene therapy in DBA/1 mice exerts an influence beyond anti-inflammatory effects. Two measures of CIA pathogenesis were investigated-namely, immunity to collagen II (CII) 245-270 peptide (the major immunodominant epitope within bovine CII) and the preferential activation of T cell Vbeta8.2 variable region receptors in arthritic DBA/1 mice. METHODS: DBA/1 mice received single periarticular injections of media or retroviral vectors containing LacZ or human TNF-R into affected arthritic paws at disease onset. Disease severity was monitored, immune responses towards the immunodominant bovine CII 245-270 and subdominant CII 334-360 peptide epitopes were assessed by ELISA, and T cell Vbeta usage was analysed by real time polymerase chain reaction for the LacZ transduced, TNF-R, and viral-free media treated control animals. The therapeutic influence of TNF-R gene transduction was compared with other groups at different times after treatment. RESULTS: Reduced disease severity was seen 15-35 days after treatment, with a concomitant increase in immunity towards the subdominant CII 334-360 peptide epitope rather than the immunodominant CII 245-270 peptide in TNF-R treated animals. Early in the disease, TNF-R treated animals demonstrated a reduction of bias towards the otherwise predominant Vbeta8.2 T cell subset. CONCLUSIONS: TNF-R gene therapy influences cellular immunity in CIA, leading to overall disease amelioration, thus suggesting that TNF inhibition may have therapeutic potential beyond the control of inflammation in RA.

Animals↗

PubMed2005

Akt inhibition upregulates FasL, downregulates c-FLIPs and induces caspase-8-dependent cell death in Jurkat T lymphocytes.

In T lymphocytes, the role of Akt in regulating Fas/Fas ligand (FasL)-mediated apoptotic signaling and death is not clearly understood. In this study, we observed that inhibition of Akt causes enhanced expression of FasL mRNA and protein and increased death-inducing signaling complex (DISC) formation with Fas-associated death domain (FADD) and procaspase-8 recruitment. Also, caspase-8 was activated at the DISC with accompanying decrease in c-FLIPs expression. FasL neutralizing antibody significantly decreased apoptotic death in the Akt-inhibited T cells. Additionally, Akt inhibition-induced Fas signaling was observed to link to the mitochondrial pathway via Bid cleavage. Further, inhibition of caspase-8 activity effectively blocked the loss of mitochondrial membrane potential and DNA fragmentation, suggesting that DISC formation and subsequent caspase-8 activation are critical initiating events in Akt inhibition-induced apoptotic death in T lymphocytes. These data demonstrate yet another important survival function governed by Akt kinase in T lymphocytes, which involves the regulation of FasL expression and consequent apoptotic signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus.

Glucose directly alters the action potential frequency of glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Glucose-excited neurons increase, and glucose-inhibited neurons decrease, their action potential frequency as glucose increases from 0.1 to 2.5 mmol/l. Glucose-excited neurons utilize the ATP-sensitive K(+) channel (K(ATP) channel) to sense glucose, whereas glucose opens a chloride channel in glucose-inhibited neurons. We tested the hypothesis that lactate, an alternate energy substrate, also regulates the action potential frequency of VMN glucose-excited and -inhibited but not nonglucosensing neurons. As expected, lactate reversed the inhibitory effects of decreased glucose on VMN glucose-excited neurons via closure of the K(ATP) channel. Although increasing glucose from 2.5 to 5 mmol/l did not affect the activity of glucose-excited neurons, the addition of 0.5 mmol/l lactate or the K(ATP) channel blocker tolbutamide increased their action potential frequency. In contrast to the glucose-excited neurons, lactate did not reverse the effects of decreased glucose on VMN glucose-inhibited neurons. In fact, it increased their action potential frequency in both low and 2.5 mmol/l glucose. This effect was mediated by both K(ATP) and chloride channels. Nonglucosensing neurons were not affected by lactate. Thus, glucose and lactate have similar effects on VMN glucose-excited neurons, but they have opposing effects on VMN glucose-inhibited neurons.

Animals↗

PubMed2004

Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice.

INTRODUCTION: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways to control certain bacterial infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra. OBJECTIVES: Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic lung infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth. METHODS: Study I. Mice with Escherichia coli MT102 [luxR-PluxI-gfp(ASV)] lung infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test the interference of furanones with quorum-sensing. Study II. Mice with lung infection by Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] were injected intravenously with furanones to evaluate their inhibiting effects on quorum-sensing. Study III. Mice with P. aeruginosa PAO1 lung infection were treated with different doses of furanones to evaluate the therapeutic effects of furanones on the lung infection. RESULTS: Furanones successfully interfered with N-acyl homoserine lactone and suppressed bacterial quorum-sensing in lungs, which resulted in decreases in expression of green fluorescent protein. Furanones accelerated lung bacterial clearance, and reduced the severity of lung pathology. In a lethal P. aeruginosa lung infection, treatment with furanone significantly prolonged the survival time of the mice. CONCLUSION: Synthetic furanone compounds inhibited bacterial quorum-sensing in P. aeruginosa and exhibited favourable therapeutic effects on P. aeruginosa lung infection.

Alginates↗

PubMed2004

Importance of the Gal alpha1-3 Gal antigen in discordant islet xenotransplantation: immunosuppression, which inhibits porcine islet xenograft rejection in ordinary mice, is equally effective in Gal-knockout mice.

BACKGROUND: Islet xenotransplantation will most likely be performed in diabetic patients treated with immunosuppressive drugs. The importance of the galactosyl alpha(1-3) galactose (Galalpha1-3Gal) antigen in immunosuppressed islet xenograft recipients has not been studied. METHODS: Fetal porcine islet-like cell clusters (ICCs) were transplanted into the renal subcapsular space of both Gal-knockout mice and ordinary mice. Transplantations were performed in untreated mice and mice immunosuppressed with cyclosporine A (CsA) plus 15-deoxyspergualin (DSG). Studies were also performed in immunosuppressed Gal-knockout mice that had been actively immunized against Galalpha1-3Gal. Evaluation was performed 12 days after transplantation using morphologic techniques. The levels of serum immunoglobulin (Ig)G and IgM to the Galalpha1-3Gal antigen or to the ICCs were determined. RESULTS: No difference in the morphologic appearance could be seen between ordinary mice and Gal-knockout mice. No deposits of IgG, IgM, or C3 could be detected. Almost no difference could be seen between immunosuppressed Gal-knockout mice and immunosuppressed ordinary mice. In immunosuppressed, immunized Gal-knockout mice, the results were similar. In ordinary mice treated with CsA+DSG, the levels of anti-Gal IgM were lower than they were in untreated mice, whereas the levels of anti-Gal IgG were similar. In Gal-knockout mice (including immunized animals) treated with CsA+DSG, the levels of anti-Gal IgG and IgM were lower than they were in untreated Gal-knockout mice. CONCLUSIONS: After renal subcapsular transplantation, antibodies against Galalpha1-3Gal have no major influence on islet xenograft rejection in the pig-to-mouse model. Immunosuppression, which inhibits rejection in the pig-to-mouse model, is equally effective when transplantation is performed across the Galalpha1-3Gal barrier.

Animals↗

PubMed2003

Selectivity in vibrationally mediated single-molecule chemistry.

The selective excitation of molecular vibrations provides a means to directly influence the speed and outcome of chemical reactions. Such mode-selective chemistry has traditionally used laser pulses to prepare reactants in specific vibrational states to enhance reactivity or modify the distribution of product species. Inelastic tunnelling electrons may also excite molecular vibrations and have been used to that effect on adsorbed molecules, to cleave individual chemical bonds and induce molecular motion or dissociation. Here we demonstrate that inelastic tunnelling electrons can be tuned to induce selectively either the translation or desorption of individual ammonia molecules on a Cu(100) surface. We are able to select a particular reaction pathway by adjusting the electronic tunnelling current and energy during the reaction induction such that we activate either the stretching vibration of ammonia or the inversion of its pyramidal structure. Our results illustrate the ability of the scanning tunnelling microscope to probe single-molecule events in the limit of very low yield and very low power irradiation, which should allow the investigation of reaction pathways not readily amenable to study by more conventional approaches.

Journal Article↗

PubMed2003

The Na+/H+ exchange inhibitor: a new therapeutic approach for hepatic ischemia injury in rats.

BACKGROUND: Na+/H+ exchanger (NHE) is one of the major mechanisms for restoring pH after ischemia-induced intracellular acidosis. However, activation of NHE during ischemia and reperfusion (I/R) is also involved in the paradoxical induction of cell injury. This study was designed to evaluate the effects of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), an NHE inhibitor, on hepatic I/R injury. METHODS: Partial hepatic ischemia was induced in male Wistar rats by cross-clamping the hepatic arterial and portal venous branches to the left lateral and median lobes of the liver for 120 minutes. The caudate and right lateral lobes were removed immediately after reperfusion. The concentrations of serum enzymes and ATP levels and energy charge in the live tissue were examined after 1-hour reperfusion. RESULT: EIPA afforded considerable protection against I/R injury, as demonstrated by decreased transaminase release and reduced histologic hepatocyte damage and increased energy charge. The 7-day survival rate was significantly improved from 15.4% to 55.6% (P <.05). CONCLUSIONS: This study shows for the first time that NHE may play an important role in the hepatic I/R injury and that EIPA should be considered as a new therapeutic approach to prevent hepatic I/R injury.

Adenosine Triphosphate↗

PubMed2003

Tacrolimus inhibits discordant islet xenograft rejection: a study in the pig-to-rat model.

The aim of the present study was to evaluate the immunosuppressive effect of tacrolimus (TAC) in discordant islet xenotransplantation. Fetal porcine islet-like cell clusters (ICCs) were transplanted under the kidney capsule in normoglycemic rats treated with TAC monotherapy, TAC plus other immunosuppressive drugs or cyclosporin A (CsA) monotherapy. Twelve or 24 days after transplantation, the extent of a cellular infiltration in the xenografts was evaluated using immunohistochemistry. In some animals, the grafts were examined for antibody and complement deposition and the levels of xenoreactive antibodies in serum were determined. In untreated rats, the xenografts were completely rejected after 12 days and no intact ICCs remained. TAC monotherapy (at 0.5 and 1.0 mg/kg b.w.) almost completely inhibited rejection for up to 12 days. In animals treated with TAC monotherapy (at 0.5 mg/kg b.w.), rejection was markedly inhibited for up to 24 days. However, the effect after 24 days was not consistent and in some grafts there were signs of rejection. The protective effect of TAC observed in this study is in contrast to the findings in rats given CsA monotherapy in which no or only a marginal effect on islet xenograft rejection was observed. Only when CsA was given at 20 mg/kg b.w., an inhibitory effect could be observed. Immunosuppression with TAC at a suboptimal dose (0.3 mg/kg b.w.) plus 15-deoxyspergualin or brequinar also had an inhibitory effect on the rejection. In animals given TAC plus mycophenolate mofetil, a protective effect was observed as well; however, this effect was not consistent.

Animals↗

PubMed2003

IFNgamma deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor Vbeta6 and Vbeta8 in arthritic joints.

BACKGROUND: Transgenic deficiency in interferon gamma (IFNgamma) or IFNgamma receptor makes resistant strains of mice bearing H-2(b) or H-2(d) susceptible to collagen induced arthritis (CIA). OBJECTIVE: To determine whether the escape from regulation of disease susceptibility at the major histocompatibility complex level involves a new use of autoimmune T cells expressing T cell receptor (TCR) Vbeta that vary from the cell populations previously identified within arthritic joints. METHODS: Arthritis was induced by a standard protocol with type II bovine collagen (CII) in complete Freund's adjuvant. Clinical features, histopathology, immunological responses, and TCR profile in arthritic joints in IFNgamma knockout C57BL/6 (B6.IFNgamma KO) mice (H-2(b)) were compared directly with those in DBA/1 mice (H-2(q)). RESULTS: 60-80% of B6.IFNgamma KO mice developed a progressive arthritis with a similar clinical course to classical CIA in DBA/1 mice. The affected joints in B6.IFNgamma KO mice had an erosive form of arthritis with similar features to joint disease in DBA/1 mice. B6.IFNgamma KO mice produced significantly higher levels of IgG2b and IgG1 autoantibodies to murine CII and showed increased proliferative response to CII compared with B6 mice. Comparable levels of interleukin 1beta and tumour necrosis factor alpha expression were detected in arthritic joints from beta6.IFNgamma KO and DBA/1 mice. B6.IFNgammaKO mice used predominantly TCR Vbeta6 and Vbeta8 in arthritic joints. This TCR Vbeta profile is similar to that found in DBA/1 mice with CIA. CONCLUSIONS: C57BL/6 mice deficient in IFNgamma production can develop arthritis that resembles classical CIA. These data suggest that IFNgamma is a key factor mediating susceptibility to CIA.

Animals↗

PubMed2002

Protein metabolism during an acute phase response in chickens.

Fractional rates of liver, muscle, plasma and acute phase portein synthesis were measured in chickens injected with saline or E. coli lipopolysaccharide (LPS). Male Single Comb White Leghorns were infused with a primed constant infusion of 15N-L-methionine and 2H5-L-phenylalanine into the portal vein for 2 h. Changes in plasma amino acid enrichment were similar for both amino acids reaching an apparent plateau by the 30 min sampling time. The enrichment of plasma protein-bound amino acid was measurable after 1 h of isotope infusion and increased linearly over 2h. LPS injection decreased free phenylalanine enrichment in the carotid artery (50%), and reduced tissue free methionine enrichment in the liver, pectoralis, and gastrocnemius by 16, 41, and 31% respectively. Isotopic enrichment of phenylalanine in liver protein, plasma protein and hemopexin increased in LPS injected birds relative to control birds. Fractional rates of muscle protein synthesis were not affected by LPS injection, however, liver protein, plasma protein, and hemopexin fractional synthesis rates increased 141, 161 and 266% respectively compared with untreated animals.

Acute-Phase Proteins↗

PubMed2002

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response.

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

Agar↗

PubMed2001

Transplantation of mouse pancreatic islets into primates--in vivo and in vitro evaluation.

BACKGROUND: Islets transplanted from other species to man has the potential to cure diabetes but whether islets are subject to hyperacute rejection after xenotransplantation is contentious. We transplanted mouse pancreatic islets of mouse beneath the primate renal capsule and assessed natural xenoantibody binding, complement activation and cell lysis in vitro. METHODS: Freshly isolated mouse islets were transplanted in a blood clot under the renal capsule of cynolmogus monkeys. The graft was removed after 24 hr for histological and ultrastructural analysis. Freshly isolated mouse pancreatic islets were analyzed in vitro by immunohistochemistry for Gal(alpha1,3)Gal and Von Willebrand factor expression and for IgG, IgM, C3, C4, and C5b-9 binding after incubation in 100% human serum. Complement mediated cell lysis was evaluated by 51Cr release assays after incubation of islets for 4 hr in human serum, plasma, and lymph with and without added neutrophils. RESULTS: Mouse islets transplanted under the renal capsule of cynomolgus monkeys were destroyed within 24 hr by a process involving necrosis with neutrophil and mononuclear cell infiltration. Gal(alpha1,3)Gal was strongly positive on only 10% of islet cells. After islet incubation in 100% human serum before frozen section, human IgG and IgM, C3, C4, and C5b-9 was deposited on islets with increased intensity in the periphery. Measurement of 51Cr release from labeled fresh islets after four hours incubation in 100% human serum showed 17% lysis and was not changed by addition of neutrophils. CONCLUSION: These results indicate that mouse islets in a primate recipient undergo rapid destruction by a process that has features similar to hyperacute rejection in vascularized organs and we propose the same term be used.

Animals↗