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In the environment of a hot plasma, as achieved in stellar explosions, capture and photodisintegration reactions proceeding on excited states in the nucleus can considerably contribute to the astrophysical reaction rate. Such reaction rates including the excited-state contribution are obtained from theoretical calculations as the direct experimental determination of these astrophysical rates is currently unfeasible. In the present study, ($\gamma$,p) and ($\gamma$,$\alpha$) reactions in the mass and energy range relevant to the astrophysical $p$ process are considered and the feasibility of measuring them with the ELISSA detector system at the future Variable Energy $\gamma$-ray (VEGA) facility at ELI-NP is investigated. The simulation results reveal that, for the ($\gamma$,p) reaction on twelve targets of $^{29}$Si, $^{56}$Fe, $^{74}$Se, $^{84}$Sr, $^{91}$Zr, $^{96,98}$Ru, $^{102}$Pd, $^{106}$Cd, and $^{115, 117, 119}$Sn, and the ($\gamma$,$\alpha$) reaction on five targets of $^{50}$V, $^{87}$Sr, $^{123,125}$Te, and $^{149}$Sm, the yields of the reaction channels with the transitions to the excited states in the residual nucleus are relevant and even dominant. It is further found that for each considered reaction, the total yields of the charged-particle $X$ may be dominantly contributed from one, two or three ($\gamma$,$X_{i}$) channels within a specific, narrow energy range of the incident $\gamma$-beam. Furthermore, the energy spectra of the ($\gamma$,$X_{i}$) channels with $0\leq i\leq 10$ are simulated for each considered reaction, with the incident $\gamma$-beam energies in the respective energy range as derived before. It becomes evident that measurements of the photon-induced reactions with charged-particle emissions considered in this work are feasible with the VEGA+ELISSA system and will provide knowledge useful for nuclear astrophysics., Comment: 11 figures, 17 pages

Disposal of long-lived fission products (LLFPs) produced in reactors has been paid a lot attention for sustainable and clean nuclear energy. Although a few transmutation means have been proposed to address this issue, there are still scientific and/or engineering challenges to achieve efficient transmutation of LLFPs. In this study, we propose a novel concept of advanced nuclear energy system (ANES) for transmuting LLFPs efficiently without isotopic separation. The ANES comprises intense photoneutron source (PNS) and subcritical reactor, which consist of lead-bismuth (Pb-Bi) layer, beryllium (Be) layer, and fuel, LLFPs and shield assemblies. The PNS is produced by bombarding radioactive cesium and iodine target with a laser-Compton scattering (LCS) γ-ray beam. We investigate the effect of the ANES system layout on transmutation efficiency by Monte Carlo simulations. It is found that a proper combination of the Pb-Bi layer and the Be layer can increase the utilization efficiency of the PNS by a factor of ~10, which helps to decrease by almost the same factor the LCS γ-beam intensity required for driving the ANES. Supposing that the ANES operates over 20 years at a normal thermal power of 500 MWt, five LLFPs including 99Tc, 129I, 107Pd, 137Cs and 79Se could be transmuted by more than 30%. Their effective half-lives thus decrease drastically from ~106 to less than 102 years. It is suggested that this successful implementation of the ANES paves the avenue towards practical transmutation of LLFPs without isotopic separation.

Lake sediment is an important carbon reservoir. However, little is known on the dynamics and sources of sediment organic carbon in the Bosten Lake. We collected 13 surface (0–2 cm) sediment samples in the Bosten Lake and analyzed total organic carbon (TOC), total nitrogen (TN), stable carbon isotopic composition in TOC (δ13Corg) and grain size. We found a large spatial variability in TOC content (1.8–4.4 %) and δ13Corg value (−26.77 to −23.98 ‰). Using a three end member mixing model with measured TOC : TN ratio and δ13Corg, we estimated that 54–90 % of TOC was from autochthonous sources. Higher TOC content (> 3.7 %) was found in the east and central-north sections and near the mouth of the Kaidu River, which was attributable to allochthonous, autochthonous plus allochthonous, and autochthonous sources, respectively. The lowest TOC content was found in the mid-west section, which might be a result of high kinetic energy levels. Our study indicated that the spatial distribution of sediment TOC in the Bosten Lake was influenced by multiple and complex processes.

Aims: To investigate the role of macrophage migration inhibitory factor (MIF) and its downstream cytokine cascade in necrotizing enterocolitis (NEC). Methods and results: The expression of MIF mRNA and protein in NEC guts was assayed by in situ hybridization and immunohistochemistry, respectively. Concentrations of MIF, interleukin (IL)-6 and IL-8 in the serum and in the supernatant of macrophage cultures were examined by ELISA. Increased expression of MIF mRNA and protein was observed in the NEC guts, mainly in the infiltrating macrophages in the mucosa and submucosal layers. Up-regulation of MIF was associated with the accumulation of macrophages and T cells. In addition, serum levels of MIF, IL-6 and IL-8 in NEC patients during the acute stage of the disease were significantly increased. The expression of MIF decreased both locally and systemically after the disease was resolved. MIF was also found to increase the secretion of IL-6 and IL-8 by macrophages isolated from healthy individuals in vitro in NEC. Conclusions: MIF acts by stimulating macrophage production of IL-6 and IL-8. This further aggravates the inflammatory process by increasing the infiltration of neutrophils and activating inflammatory cells. The results of this study suggest that MIF plays an important role in the pathogenesis of NEC and may serve as a target for therapeutic intervention in NEC.

Background & Aims: Macrophage migration inhibitory factor (MIF) has been shown to play a pivotal role in inflammatory and immune-mediated diseases. This study investigates the role of MIF in gastric inflammation. Methods: Expression of MIF was examined in a rat gastric ulcer model induced by acetic acid, and the functional role of MIF in acute gastric ulcer was investigated by administration of a neutralizing anti-MIF antibody. Results: MIF messenger RNA and protein were markedly up-regulated in acute gastric ulcer, which correlated with the accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of inflammation. Macrophages, like neutrophils, were the major inflammatory cells infiltrating the ulcer base and they strongly expressed inducible nitric oxide synthase. However, macrophages, not neutrophils, were a rich source of MIF production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the neutralizing anti-MIF antibody significantly inhibited the marked up-regulation of MIF, tumor necrosis factor a, inducible nitric oxide synthase, and intercellular adhesion molecule-1. This was associated with the marked inhibition of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and activation, thus reducing ulcer sizes and attenuating ulceration. Conclusions: This study has shown that MIF was markedly up-regulated during acute gastric ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is a key inflammatory mediator and plays a pathogenic role in gastric inflammation.

The effects of postmortem aging time (2, 9, and 16 days) and endpoint cooking temperature (60, 70, and 80C) on the eating characteristics of pork longissimus (LD) muscle were evaluated. Gilts (n=60) were from 4 different commercial hybrid genotypes (15 pigs/genotype) selected to produce a range of intramuscular fat. Results suggest that LD muscle from genotype 2, which was selected for its propensity to increase marbling had higher intramuscular fat content, tenderness and juiciness scores than that from the other genotypes (P < 0.05). Increasing aging time from 2 to 16 days increased sensory juiciness and tenderness, and decreased instrumental shear force and cooking loss (P < 0.05). Aging for nine days decreased shear force (P < 0.05) but had no effect on tenderness and juiciness scores and cooking loss when compared to 2 days aging. Increasing endpoint temperature increased cooking loss and shear force, and decreased tenderness (P < 0.05) and juiciness.

Consumers (n = 116) evaluated color (pink intensity), appearance (wet/dry), overall acceptability and purchase intent of normal, PSE and DFD pork loin slices in PVC and in vacuum packages. Packaging x muscle condition affected (p < 0.05) appearance, overall acceptability and consumer purchase intent of pork slices. Color differences were perceptible to consumers between packaging treatments. PVC-packaged pork was pinker than vacuum-packaged pork. Vacuum-packaged, PSE pork appeared drier than PVC-packaged PSE pork. Normal pork was more acceptable than PSE pork regardless of packaging. DFD pork acceptability was not different from that of normal pork when vacuum packaged. In general purchase intent paralleled consumer evaluation of overall acceptability. Instrumental color data and pH for samples evaluated are also presented.

Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 microg) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1-2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2-3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 x 10(4) genome equivalents of HEV, regardless of the genotype. After challenge with 5 x 10(5) genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.

On the basis of amino acid (aa) sequence of the tandem repeat 133-158-20-34-133-158 which consisted of aa 133-158 of VP1 and aa 20-34 of VP4 of Foot-and-mouth disease virus (FMDV) type Asia 1 a recombinant prokaryotic expression vector pAS1-P encoding a fusion protein and eukaryotic expression vectors pAS1-E and pAS1-EdeltaCpG-ODN representing DNA vaccines were constructed. Guinea pigs immunized with these vaccines showed both neutralizing antibody and T cell proliferation responses. FMDV challenge tests for the first time showed that the recombinant fusion protein and pAS1-E and pAS1-EdeltaCpG-ODN vaccines protected 86%, 60% and 43% of guinea pigs from FMDV type Asia1 challenge, respectively. The results also indicated that the immune response of animals treated with the vector pAS1-E containing an oligodeoxynucleotide (ODN), which consisted of immunostimulatory cytosine-phosphate-guanosine (CpG) motifs, was augmented by CpG ODN.

Findings The serum 25(OH)D level of CAD patients was 18.2 10.6 ng/ml. The SYNTAX scores were 27.8 8.5. In a multivariate linear regression analysis (adjusted for age, high-sensitivity C-reactive protein, SYNTAX score, parathyroid hormone, body mass index, haemoglobin and creatinine), the serum 25(OH)D level showed a negative correlation with SYNTAX score and high-sensitivity C-reactive protein (hsCRP) level. Logistic regression analysis identified 25(OH)D as an independent factor related to high SYNTAX scores. Patients whose vitamin D levels were in the lowest 25(OH)D category ( 30 ng/ml).

We report controllable azimuthons of four-wave mixing (FWM), which can be modulated by several parameters in experiment. The spot number, splitting depth, rotation angular velocity and direction of such azimuthons can be controlled by the frequency and intensity of the FWM signal or the dressing field through the cross-phase modulation due to atomic coherence. The intensity gain of the azimuthons can be modulated by frequency detuning through quantum parametric amplification. The quantum correlated FWM vortex is observed in experiment. We also discuss the applications of such controllable azimuthons in all-optical circulators, multiplexers (demultiplexers), routers, cross-connects and optical amplifiers.

Local proliferation of macrophages occurs within both the glomerulus and the interstitium in severe forms of human and experimental glomerulonephritis and plays an important role in amplifying renal injury. Macrophage colony-stimulating factor (M-CSF) is thought to be the growth factor driving this local macrophage proliferation. Previous studies have found that glomeruli are the predominant source of M-CSF production. However, this is difficult to reconcile with the prominent macrophage accumulation and proliferation seen in the interstitial compartment in glomerulonephritis. To address this issue, we localized M-CSF expression in rat models of glomerular versus tubulointerstitial injury and examined its relationship to local macrophage proliferation.M-CSF expression (Northern blotting, in situ hybridization, immunostaining, Western blotting) and local macrophage proliferation (double immunostaining) was examined in normal rat kidney on days 1 and 14 of rat anti-glomerular basement membrane (anti-GBM) glomerulonephritis and on day 5 following unilateral ureteric obstruction.M-CSF mRNA and protein expression were identified in small numbers of glomerular podocytes, approximately 25% of cortical tubules, and most medullary tubules in normal rat kidney. Northern blotting showed a significant increase in whole kidney M-CSF mRNA in rat anti-GBM glomerulonephritis. Up-regulation of glomerular and, most prominently, tubular M-CSF production was confirmed by three independent methods: in situ hybridization, immunostaining, and Western blotting. The increase in M-CSF expression colocalized with local macrophage proliferation (ED1+PCNA+ cells) in both the glomerulus and tubulointerstitium. On day 5 after ureter ligation, there was a significant increase in tubular M-CSF mRNA and protein expression in the obstructed kidney, with no change in glomerular M-CSF. In parallel with M-CSF expression, macrophage accumulation and proliferation was prominent in the interstitium, but was absent from glomeruli.The tubular epithelial cell is the major site of M-CSF production within the injured kidney. Indeed, substantial macrophage accumulation and local proliferation can occur in the tubulointerstitium in the absence of glomerular inflammation. These results suggest that M-CSF production within the kidney, particularly by tubular epithelial cells, plays an important role in regulating local macrophage proliferation in experimental kidney disease.

Hyperuricemia frequently complicates cyclosporine (CSA) therapy. The observation that longstanding hyperuricemia is associated with chronic tubulointerstitial disease and intrarenal vasoconstriction raised the hypothesis that hyperuricemia might contribute to chronic CSA nephropathy.CSA nephropathy was induced by the administration of CSA (15 mg/kg/day) for 5 and 7 weeks to rats on a low salt diet (CSA group). The effect of hyperuricemia on CSA nephropathy was determined by blocking the hepatic enzyme uricase with oxonic acid (CSA-OA). Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA). Histological and functional studies were determined at sacrifice.CSA treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular injury and striped interstitial fibrosis. CSA-OA treated rats had higher uric acid levels in association with more severe arteriolar hyalinosis and tubulointerstitial damage. Intrarenal urate crystal deposition was absent in all groups. Both CSA and CSA-OA treated rats had increased renin and decreased NOS1 and NOS3 in their kidneys, and these changes are more evident in CSA-OA treated rats.An increase in uric acid exacerbates CSA nephropathy in the rat. The mechanism does not involve intrarenal uric acid crystal deposition and appears to involve activation of the renin angiotensin system and inhibition of intrarenal nitric oxide production.

By Agrobacterium-mediated method, the cotyledonary petiole of good quality rape variety H165 was transformed with plant expression vector pBLGC which constitutively express beta-1,3-glucanase and chitinase genes. We obtained some Kanamycin(Kan)-resistant regenerational green shoots, with these shoots, PCR identification was conducted. Results showed that 30% green shoots which grew in medium of Kan 15 mg/L and 53% green shoots in Kan 25 mg/L had positive reaction. We also made dot blot analysis with those green shoots, some of them gave positive signal, indicating that the foreign genes had integrated into rape genome. Fungal challenge of these transgenic plants showed that some plants were much more resistant to Sclerotinia sclerotiorium than non-transgenic control plants.

Plant bivalent expression vector pBLGC for basic tobacco beta-1, 3-glucanase and bean chitinase genes were constructed, and the tobacco tissue was transformed. Transgenic tobacco plants were carried out for analysis by PCR, PCR-Southern blot, Dot blot, Western blot, etc., and the results showed that some transgenic plants gave strong positive signal, it suggested that foreign genes have been integrated into tobacco genome, and expressed correctly. Fungal challenge with Alternaria alternata showed that transgenic plants were much more resistant to this pathogenic fungus.

Macrophage migration inhibitory factor (MIF) plays a pivotal role in immune-mediated diseases. Despite the long-standing association of MIF with the delayed-type hypersensitivity response, the potential role of MIF in allograft rejection is unknown.MIF expression was assessed by in situ hybridization and immunohistochemistry staining in 62 biopsies of human renal allograft rejection and in normal human kidney.MIF mRNA and protein is constitutively expressed in normal kidney, being largely restricted to tubular epithelial cells, some glomerular epithelial cells, and vascular smooth muscle cells. In both acute and chronic renal allograft rejection, there was marked up-regulation of MIF mRNA and protein expression by intrinsic kidney cells such as tubular epithelial cells and vascular endothelial and smooth muscle cells. There was also MIF expression by infiltrating macrophages and T cells. Of note, macrophage and T cell infiltrates were largely restricted to areas with marked up-regulation of MIF expression, potentially contributing to the development of severe tubulitis and intimal or transmural arteritis. Quantitative analysis found that increased MIF expression in allograft rejection gave a highly significant correlation with macrophage and T cell accumulation in both the glomerulus and interstitium (P0.001). In addition, the number of MIF+ tubules and interstitial MIF+ cells correlated significantly with the severity of allograft rejection (P0.01), and the loss of renal function (P0.01). In contrast, no up-regulation of renal MIF expression and no leukocyte accumulation was seen in allograft biopsies without evidence of rejection.This is the first study to demonstrate that local MIF expression is up-regulated during allograft rejection. The association between up-regulation of MIF expression, macrophage and T cell infiltration and the severity of renal allograft rejection suggests that MIF may be an important mediator in the process of allograft rejection.

Regulation of T-cell traffic and function in the adult rat testis was assessed following treatment with the specific Leydig cell cytoxin, ethane dimethane sulfonate (EDS), and s.c. testosterone implants to prevent Leydig cell recovery. The distribution of T-cell subsets in the testis was determined immunohistochemically using stereological techniques. Testicular T cell-inhibiting activity in the interstitial fluid was measured using a phytohemagglutinin-activated rat thymocyte proliferation bioassay. The mostly cytotoxic CD8+ T-cell subset predominated over the CD4+ (regulatory) T-cell subset in the normal rat testis. Destruction of the Leydig cells caused a rapid preferential increase in testicular CD4+ T cells, which was followed by an increase in both the CD8+ subset and T cell-inhibiting activity in the Leydig cell-deficient testis. After Leydig cell recovery, there was a significant shift toward the CD8+ T-cell subset in the EDS-treated testis but not in the EDS-treated/testosterone-implanted testis. Total T-cell numbers and inhibitory activity in the testis returned to control levels regardless of whether the Leydig cells were allowed to recover. The level of inhibitory activity was closely related to the number of CD8+ T cells in the testis across all experimental groups, but it showed no relationship with pituitary hormones, macrophage numbers, or intratesticular testosterone levels. The data suggest that 1) cytotoxic lymphocytes have a potentially significant role in testicular function and 2) T cell-inhibiting activity in the testis interstitium is not substantially affected by changes in pituitary hormones or Leydig cell function, but appears to be related to local changes in immune activity.

This study examined whether osteopontin (OPN), a molecule with monocyte chemotactic and adhesive activity, participates in macrophage-mediated renal disease, Accelerated anti-glomerular basement membrane glomerulonephritis was induced in groups of six rats. Animals were treated with a neutralizing anti-OPN or an irrelevant control antibody over days 0-7 (induction phase) or days 7-14 (established disease). Administration of the control antibody had no effect on the severity of the disease. In contrast, anti-OPN treatment significantly reduced glomerular injury (urinary protein excretion) and prevented a loss of renal function (creatinine clearance) during the induction of disease. This was accompanied by a significant reduction in renal macrophage and T-cell accumulation, T-cell activation, and histological injury (glomerular hypercellularity, segmental lesions, crescents, and tubulointerstitial lesions). An important finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reduction in glomerular injury and recovery of renal function in association with inhibition of macrophage and T-cell accumulation, T-cell activation, and histological damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in the kidney. Interestingly, anti-OPN treatment significantly reduced skin swelling and leukocyte infiltration in the delayed type hypersensitivity response. However, anti-OPN treatment had no effect on the humoral immune response. In summary, this study has demonstrated that OPN plays a functional role in macrophage and T-cell accumulation and renal damage in both the induction and progression of a rat model of crescentic glomerulonephritis. Thus, OPN may be of pathological importance in human glomerulonephritis and in cell-mediated immune diseases generally.

Local macrophage proliferation has been shown to be a major mechanism of macrophage accumulation in several immunologically-induced animal models of renal diseases. This study has explored whether local proliferation of macrophages and myofibroblasts contribute to their accumulation in rat remnant kidney model and investigated the role of angiotensin II (Ang II) in these cellular pathological events by blocking the angiotensin II activity with ramipril, and angiotensin converting enzyme (ACE) inhibitor, or valsartan, an Ang II type 1 receptor antagonist. There was local proliferation of macrophages and myofibroblasts within renal parenchyma following renal ablation, contributing significantly to macrophage and myofibroblasts accumulation, renal dysfunction and fibrosis. Both treatment resulted in inhibition of local proliferation of macrophages and myofibroblasts and this was associated with attenuation of renal injury. In conclusion, inhibition of local macrophage and myofibroblast proliferation may be an important mechanism by which Ang II blockade attenuated renal injury following renal ablation.

Interleukin-1 (IL-1) is a pro-inflammatory cytokine that exerts a wide range of biological effects. The recently identified IL-1 receptor antagonist (IL-1ra) has provided a tool for blocking IL-1 activity in vivo, leading to a detailed understanding of the role of this cytokine in the inflammatory response. The importance of IL-1 production in glomerulonephritis has been shown by the ability of IL-1ra treatment to suppress the induction and progression of experimental crescentic glomerulonephritis. Although further studies are required, IL-1ra treatment is an attractive adjunct therapy for patients with progressive glomerulonephritis.

The influence of the Leydig cells on the leukocyte population of the testis was investigated. Leydig cells were destroyed by ethane dimethane sulfonate (EDS) treatment in adult male rats, with or without low-dose s.c. testosterone implants to prevent Leydig cell recovery. Leukocytes were counted in perfusion-fixed frozen testis sections, by use of cell-specific monoclonal antibodies (mAbs) with immunoperoxidase detection, or toluidine blue staining. The majority (81%) of testicular leukocytes (OX1+) were immunopositive for the resident macrophage-specific mAb, ED2, and/or the monocyte/macrophage/dendritic cell mAb, ED1. The remaining leukocytes were principally T lymphocytes (R73+). B lymphocytes (OX33+) and metachromatic mast cells were not observed in the normal testis. Treatment with EDS caused a transient increase in ED1+, ED2+, and R73+ cell numbers in the testis, although other evidence of an inflammatory reaction, such as increases in major histocompatibility complex class II antigen, interleukin-2 receptor expression, or capillary permeability, were not observed. At 21 days after EDS treatment, there was a significant decline in macrophage numbers (to approximately 50% of control testis), and T lymphocytes returned to pretreatment levels. After Leydig cell recovery (41 days after treatment), macrophages also returned to pretreatment levels in EDS-treated rats, but remained reduced in EDS-treated animals with testosterone implants. In addition, EDS treatment stimulated a progressive increase in intertubular mast cells, which was significantly inhibited in the testosterone-implanted rats. The data indicate that numbers of testicular macrophages and mast cells, but not of lymphocytes, within the adult rat testis are directly or indirectly regulated by the Leydig cells.

The functional importance of ICAM-1 and its ligands, the beta 2-integrins, in leukocytic accumulation in pulmonary injury has been recently demonstrated in experimental models of lung disease. However, the exact location of these adhesion molecules remains unknown. In the current study we have used immunogold ultrastructural techniques to define the precise location of ICAM-1 in the lung and its interaction with beta 2-integrin expressing leukocytes in the early stages of experimental Goodpasture's (GP) syndrome in the rat. In normal animals there is strong constitutive ICAM-1 expression on the luminal surface of the alveolar epithelium that is confined to type I cells and completely absent from type II cells. Constitutive expression of ICAM-1 on the pulmonary capillary endothelium is comparatively weak. In GP syndrome there is an increase in ICAM-1 expression, which is still confined to the alveolar type I epithelial cells and capillary endothelium. This is associated with an early (1.5 hours) influx of CD18 expressing polymorphonuclear leukocytes, which are seen migrating into alveoli and the pulmonary interstitium. There is a later (6-12 hours) influx of CD11a/CD18 expressing macrophages which are present in the interstitium and in large numbers in the alveolar spaces, where they are very closely apposed to and adherent to the alveolar epithelium. This is the first study to demonstrate the precise ultrastructural location of ICAM-1 in the normal rat lung and in disease. In vivo administered antibody to ICAM-1 gains access to the extravascular sites within the lung, in particular the surface of alveolar type I epithelial cells, and this raises the possibility that beneficial effects of such antibodies may extend beyond their ability to inhibit interactions between leukocytes and endothelial cells.

There is good evidence from experimental studies that glomerular macrophages are important in acute renal injury and an increasing acceptance that they also play a role in chronic glomerular injury by stimulating mesangial cell proliferation and glomerulosclerosis. However, it is now evident that the contribution of macrophages and T cells within the interstitium must be taken into account. Indeed, if it is proved that progressive renal injury occurs via interstitial DTH mechanisms, regardless of the nature of the initial glomerular insult, then such mechanisms may provide a suitable target for the development of novel therapeutic strategies.

To investigate the role of leukocytes in the pathogenesis of pulmonary injury after antibody deposition on the alveolar basement membrane, we have induced experimental Goodpasture's syndrome in the rat using passive accelerated anti-glomerular basement membrane (GBM) disease. Animals were immunized with normal rabbit IgG and given either rabbit anti-rat GBM serum or normal rabbit serum (control) 5 days later. In this model, leukocytic infiltration, severe hemorrhage, and granulomatous-like lesions developed in the lung, while a rapidly progressive glomerulonephritis was evident in the kidney. Within 30 minutes of injection of anti-GBM serum, strong linear deposition of antibody on both glomerular and alveolar basement membranes was evident. In the lung, a transient influx of polymorphonuclear cells during the first 12 hours was closely followed by macrophage infiltration, with T cell infiltration not evident until day 3. Pulmonary hemorrhage correlated with ED1+ macrophage infiltration (p less than 0.001), but not with OX-19+ T cell accumulation. Many activated mononuclear cells were found in the lung infiltrate from day 14 onward and were associated with areas of tissue damage. This study demonstrates the feasibility of using passive accelerated anti-GBM disease as a model of Goodpasture's syndrome, and suggests that inflammatory macrophages are the major cellular participants in progressive pulmonary injury after antibody deposition.