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PubMedDate not supplied

Characterization of infiltration rates from landfills: supporting groundwater modeling efforts.

The purpose of this paper is to review the literature to characterize infiltration rates from landfill liners to support groundwater modeling efforts. The focus of this investigation was on collecting studies that describe the performance of liners 'as installed' or 'as operated'. This document reviews the state of the science and practice on the infiltration rate through compacted clay liner (CCL) for 149 sites and geosynthetic clay liner (GCL) for 1 site. In addition, it reviews the leakage rate through geomembrane (GM) liners and composite liners for 259 sites. For compacted clay liners (CCL), there was limited information on infiltration rates (i.e., only 9 sites reported infiltration rates.), thus, it was difficult to develop a national distribution. The field hydraulic conductivities for natural clay liners range from 1 x 10(-9) cm s(-1) to 1 x 10(-4) cm s(-1), with an average of 6.5 x 10(-8) cm s(-1). There was limited information on geosynthetic clay liner. For composite lined and geomembrane systems, the leak detection system flow rates were utilized. The average monthly flow rate for composite liners ranged from 0-32 lphd for geomembrane and GCL systems to 0 to 1410 lphd for geomembrane and CCL systems. The increased infiltration for the geomembrane and CCL system may be attributed to consolidation water from the clay.

Fresh Water↗

PubMed2000

Local infiltration with NSAIDs for postoperative analgesia: evidence for a peripheral analgesic action.

BACKGROUND: In order to investigate the evidence for a peripheral analgesic effect of local infiltration with nonsteroidal antiinflammatory drugs (NSAIDs) in postoperative pain, we conducted a systematic review. METHODS: Randomised controlled and double-blind trials were evaluated. Outcome measures were pain scores, the use of supplementary analgesics, and time to first analgesic request. Efficacy was estimated by significant difference (P<0.05) as reported in the original reports and by calculation of the weighted mean difference of pain scores between treatment groups. RESULTS: Sixteen studies with data from 844 patients were considered appropriate for analysis. The NSAIDs were administered as intra-articular injections, as components of intravenous regional anaesthesia (IVRA), and by wound infiltration and were compared with systemic administration or placebo. In the four studies comparing intra-articular NSAIDs with systemic administration a statistically significant effect in favour of intraarticular NSAIDs was found. Only one study compared IVRA NSAID with systemic administration, showing a significant effect in favour of IVRA administration. No more than two of the five studies comparing intrawound NSAIDs with systemic administration showed significant effect after intrawound administration. Most of the studies comparing local infiltration with placebo showed significant effect in favour of local infiltration. CONCLUSION: There is evidence for a clinically relevant peripheral analgesic action of intra-articular NSAIDs while results of IVRA and wound infiltration with NSAIDs in postoperative pain are inconclusive. Trials without a systemic control group were not considered to provide evidence for a local effect.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells.

BACKGROUND: Acral pseudolymphomatous angiokeratoma of children (APACHE) is a disorder characterized clinically by red nodules and histopathologically by a massive subepidermal lymphohistiocytic infiltrate. Although it was initially thought to be a vascular nevus, it has never been regarded as a pseudolymphoma. CASE REPORT: We report a 7-year-old-girl with small red nodules on the dorsum of the right foot and a 73-year-old man with asymptomatic brown-red nodules on the lower extremities. RESULTS: Histopathologic examination revealed a massive lymphohistiocytic infiltrate with plasma cells, some eosinophils, or a multinucleated giant cell immediately beneath the epidermis. Thick-walled vessels were observed in the infiltrate. These characteristics are identical to those of acral pseudolymphomatous angiokeratoma of children. The infiltrate was composed mainly of equal numbers of CD4+ or CD8+ T cells and equal numbers of B cells stained for kappa or lambda light chains. PCR amplification of rearranged immunoglobulin heavy chain genes or T-cell receptor gamma genes showed no evidence of clonality, suggesting that these infiltrates were polyclonal both for B and T cells. CONCLUSIONS: Our data support the idea that this disorder represents a reactive process. The modified term 'papular angiolymphoid hyperplasia' would define this disorder more appropriately.

Aged↗

PubMed2000

Lipopolysaccharide-induced cytokine and receptor expression and neutrophil infiltration in the liver of osteopetrosis (op/op) mutant mice.

BACKGROUND/AIMS: Mice homozygous for the osteopetrosis (op) mutation are genetically deficient in macrophage colony-stimulating factor (M-CSF/CSF-1) and are characterized by defective differentiation and function of macrophages. The aim of this study is to assess the contribution of M-CSF to lipopolysaccharide (LPS)-induced cytokine expression and neutrophil infiltration in the liver. METHODS: We investigated the effects of LPS administration in M-CSF-deficient op/op mutant mice. The expression of cytokines and receptors in the liver was studied by immunohistochemistry and RT-PCR. Neutrophil infiltration in the liver was also examined. RESULTS: After LPS administration, cytokine production and expression of LPS receptors, such as CD14 and scavenger receptor class A (MSR-A), were induced at lower levels in op/op mice than those in littermate mice. Neutrophil infiltration in the liver of op/op mice did not differ significantly from that of littermate mice. Anti-IL-8 receptor homologue and anti-C5a receptor antibody reduced the number of infiltrating neutrophils. CONCLUSIONS: These findings indicate that deficient macrophage activation following LPS injection in op/op mice is associated with decreased expression of CD14 and MSR-A in the liver. Thus, M-CSF plays a critical role in LPS-induced macrophage activation but does not exert a dominant role in neutrophil infiltration in the liver.

Animals↗

PubMed1990

Squamous cell carcinoma: infiltrating monocyte/macrophage subpopulations express functional mature phenotype.

Biopsies from 26 patients with advanced stage squamous cell carcinoma of the head and neck were investigated to determine the intensity of the inflammatory cellular infiltrate and the expression of leucocyte antigens. Mononuclear cell infiltration varied considerably between the individual patients and also within the tumour. Tumour-infiltrating cells consisted mainly of T lymphocytes and monocytes (Mo)/macrophages (M phi). Staining procedure with monoclonal antibodies (moabs) against Mo/M phi revealed different clusters of antigen expression: (1) moabs 27E10 and a-CD35 detected a subgroup of Mo/M phi with particular staining of perivasal Mo; (2) moab a-CD1 stained preferentially cells in tumour cell clusters; (3) moabs that reacted with cells of either typical M phi or dendritic morphology throughout the tumour-tissue: a-Fc gamma receptor I-III, a-class II antigens, a-CD4, Rm3/1, a-CD36 and 25F9. Thus, the majority of tumour-infiltrating mononuclear phagocytes were found to possess a rather mature phenotype. The number of Mo/M phi with mature phenotype within the tumours correlated with T lymphocyte infiltration in the tissue.

Antigens, CD↗

PubMed1995

Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex.

The contribution of the immune system to the pathogenesis of ischemic lesions is still uncertain. We have analyzed leukocyte infiltration in photochemically induced focal ischemia of the rat parietal cortex by immunocytochemistry. Between 1 and 2 days after photothrombosis, CD5+ T cells adhered to subpial and cortical vessels and infiltrated the ischemic lesion prior to macrophages. By day 3 numerous T cells and some macrophages, whose number increased further between day 3 and day 7, had infiltrated the border zone around the lesion sparing the center. In addition, CD5-/CD8+ lymphocytes that probably represent natural killer cells were found. Intercellular adhesion molecule-1 (ICAM-1) was expressed on endothelial cells on days 1 and 2 and in the border zone on infiltrating leukocytes from day 3 to day 7. Starting on day 7, macrophages infiltrated the core of the lesion to remove debris. When the entire lesion was covered by macrophages at day 14, the number of T cells had decreased and ICAM-1 immunoreactivity was no longer found in or around the infarct. In conclusion, our study shows that ischemic lesions can lead to a local immune reaction in the CNS. Thus, blocking of lymphocyte-derived cytokines or cell adhesion molecules may provide a new approach to confining the sequelae of stroke.

Animals↗

PubMed1996

Monocyte chemoattractant protein 1 mediates glomerular macrophage infiltration in anti-GBM Ab GN.

Monocyte chemoattractant protein 1 (MCP-1) is a C-C chemokine with potent monocyte chemotactic and activating properties that may contribute to glomerular macrophage infiltration in anti-GBM Ab GN. We have previously reported increased glomerular steady state expression of MCP-1 mRNA relative to GAPDH mRNA in the heterologous phase of experimental anti-GBM Ab GN. In this report, we expand upon these data by demonstrating that the increase in MCP-1 mRNA correlated with MCP-1 protein expression at 24 hours that was determined with an ELISA (2069 +/- 147 pg/mg glom lysate). This increase in MCP-1 expression was associated with glomerular monocyte/ macrophage infiltration which peaked at 24 hours (8.2 +/- 1.0 ED-1 cells/glom). The site of MCP-1 mRNA production was localized by combining immunohistochemistry with in situ hybridization. The majority of cells which expressed MCP-1 mRNA at three hours were intrinsic glomerular cells, while 55% of the cells that expressed MCP-1 mRNA at 15 hours were monocytes/macrophages. To determine if MCP-1 affected glomerular macrophage infiltration, rats with alpha-GBM Ab GN were administered a polyclonal neutralizing Ab to rat MCP-1. This resulted in a 38% decline in glomerular macrophage infiltration (3.3 +/- 0.3 vs. 1.8 +/- 0.2 ED-1 cells/glom, P = 0.0001) that was associated with a 45% reduction in urinary protein excretion (260 +/- 53 vs. 162 +/- 46 mg/d, P = 0.0001). These data demonstrate an important role for MCP-1 in the pathogenesis of glomerular macrophage infiltration in anti-GBM Ab GN.

Animals↗

PubMed2001

Sex steroids influence pancreatic islet hypertrophy and subsequent autoimmune infiltration in nonobese diabetic (NOD) and NODscid mice.

Female nonobese diabetic (NOD) mice more frequently develop autoimmune diabetes than NOD males. Orchidectomy of the latter aggravates insulitis and diabetes. Because clear differences in immune function have not been observed between prediabetic females and males, before or after castration, we hypothesized that sex-related differences in diabetes incidence are related to target organ-specific actions of sex steroids. Previously, we showed that prediabetic NOD females develop hyperinsulinemia and subsequently mega-islets. Infiltration of the first inflammatory leukocytes is predominantly associated with these mega-islets. Here, we determined the relationship between sex hormones, mega-islet formation, and infiltrating cells in NOD and nonobese diabetic/severe combined immune-deficient (NODscid) mice. Mega-islet formation was reduced in NOD males compared with NOD females, and orchidectomy increased it, indicating a relationship between androgen levels and mega-islet formation. Moreover, enhanced mega-islet formation in castrated NOD males was associated with increased numbers of infiltrating leukocytes. Castrated NODscid males also exhibited increased mega-islet formation and dendritic cell infiltration, indicating that lymphocytes are not required for castration-induced effects. In conclusion, we show that androgens influence pancreatic islets and autoimmune infiltration in NOD and NODscid mice. This suggests that the gender difference in diabetes incidence in NOD mice is related to target organ-specific androgen effects.

Animals↗

PubMed2005

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma.

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.

Adipokines↗

PubMed2006

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8(+) or CD4(+) lymphocyte infiltration. Although the level of infiltration by CD8(+) T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8(+) and 'high' CD4(+) T-cell infiltration was significantly higher than that for the other groups (log-rank test, P=0.006). Multivariate analysis indicated that concomitant high CD8(+) and high CD4(+) T-cell infiltration was an independent favourable prognostic factor (P=0.0092). In conclusion, the presence of high levels of both CD8(+) T cells and CD4(+) T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Adult↗

PubMed2002

Contribution of endothelin-1 to renal activator protein-1 activation and macrophage infiltration in aldosterone-induced hypertension.

Aldosterone-induced hypertension is associated with renal damage that may be mediated by endothelin-1 (ET-1). We evaluated whether inflammatory cell infiltration and DNA-binding activity of the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) were increased in kidneys from aldosterone-infused rats. The role of ET-1 in these processes was evaluated by treating rats with the ET(A)-receptor blocker, BMS 182874. Rats were infused with aldosterone (0.75 microg/h) via a mini-osmotic pump and were given 1% NaCl in the drinking water in the absence and presence of BMS 182874 or of the aldosterone receptor blocker, spironolactone. Renal sections were used to assess inflammatory cell infiltration, which was identified immunocytochemically using monoclonal antibodies against macrophages (ED1+). Electrophoretic mobility shift assays evaluated the DNA-binding activity of NF-kappa B and AP-1 in renal tissue. Systolic blood pressure (BP) was increased in the aldosterone-infused group compared with controls (123+/-6 versus 110+/-10 mmHg, P<0.05). BMS 182874 and spironolactone significantly decreased BP (P<0.05). Macrophage infiltration was increased in the kidneys of aldosterone-infused rats compared with controls. Renal binding activity (arbitrary units) of AP-1, in contrast with that of NF-kappa B, increased in aldosterone-infused rats compared with control rats (AP-1, 4.2+/-0.3 versus 1.0+/-0.1, P<0.05; NF-kappa B, 1.6+/-0.5 versus 1.2+/-0.5). BMS 182874 and spironolactone decreased macrophage infiltration (by 70% and 50% respectively) and AP-1 binding activity (1.0+/-0.3 and 0.8+/-0.3 respectively). In conclusion, kidneys from aldosterone-infused rats exhibited macrophage infiltration and increased AP-1 DNA-binding activity. These processes were attenuated by BMS 182874. Our findings suggest that renal damage in aldosterone-dependent hypertension is associated with inflammatory processes that are mediated in part via ET-1.

Aldosterone↗

PubMed1996

Gastric mucosal infiltration by Helicobacter pylori favours bacterial survival after treatment.

BACKGROUND: Although a number of patient and bacterial factors have been identified as predictors of treatment failure in Helicobacter pylori-associated gastritis, the causes of lack of response to treatment have not been fully elucidated. We hypothesized that bacterial infiltration of the gastric mucosa might be one of the factors responsible for treatment failure in patients harbouring the bacterium. METHODS: We studied 182 patients with gastritis who underwent anti-H. pylori treatment with different drugs. Gastric biopsies obtained at endoscopy, were examined for electron microscopic features of infiltration and damage. Patients were assigned to different treatment groups, and endoscopy, evaluation of H. pylori status and electron microscopy were repeated at least 4 weeks after the end of treatment. RESULTS: The overall H. pylori eradication rate was 65%. Eradication was achieved more frequently in patients without electron microscopic features of infiltration (85%), than in those patients with the bacteria deeply embedded into the gastric mucosa (45%; P < 0.0001). No treatment appeared to be clearly superior for patients with the highest degree of mucosal infiltration. CONCLUSIONS: Bacterial mucosal infiltration may facilitate the survival of H. pylori during antibacterial treatment; moreover, electron microscopy may be helpful to identify patients potentially unresponsive to anti-H. pylori treatment.

Adolescent↗

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↗

PubMed2001

Ordered array of dendritic cells and CD8+ lymphocytes in portal infiltrates in chronic hepatitis C.

AIMS: Despite the importance of dendritic cells in stimulating primary and secondary immune responses by presenting antigens to T-lymphocytes in draining lymph nodes and peripheral tissues, respectively, very limited information is available on the presence and localization of these cells in hepatitis C virus (HCV)-related chronic active hepatitis. Therefore, we addressed the ultrastructure, immunophenotype, distribution and relationships to lymphatics of dendritic cells in portal infiltrates of this disease. METHODS AND RESULTS: Part of percutaneous diagnostic liver biopsies (Knodell's histological assessment index: 9-13) was processed for electron microscopy and for immunohistochemical detection of immune system cell membrane antigens and of the lymphatic endothelium marker podoplanin. In portal infiltrates, cells with electron microscopical and cell marker features of dendritic cells and expressing the activation markers CD54, CD80, CD83 and CD86 were organized in a discontinuous network, that embedded CD8+ lymphocytes in close contact with dendritic cells and came in contact with hepatocytes, sometimes infiltrating beyond the limiting plate. Also, dendritic cells were found within newly formed lymphatic capillaries in thin, infiltrated septa among hepatocytes. CONCLUSIONS: This evidence strongly suggests a critical role of dendritic cells and newly formed lymphatics in the pathogenesis and organization of the immune infiltrate that characterizes HCV-related chronic active hepatitis.

Adult↗

PubMed2003

Inclusion body myositis: clonal expansions of muscle-infiltrating T cells persist over time.

Inclusion body myositis (IBM) is a chronic inflammatory myopathy. The muscle histology is characterized by infiltration of T cells, which invade and apparently destroy muscle fibres. This study was performed to investigate whether predominant clones of muscle-infiltrating T cells are identical in different muscles and whether they persist over time in IBM. By reverse transcriptase-polymerase chain reaction, 25 T-cell receptor (TCR) variable beta (Vbeta) chain families and the complementarity-determining region 3 (CDR3) of the TCR were analysed in two different muscle biopsies of four patients with IBM. In two of the patients, the muscle biopsies were obtained from different muscles at one time point, whereas in two patients, the second biopsy was obtained 9 years after the first biopsy. T cells expressing predominant Vbeta families were analysed for clonality by fragment length analysis of the CDR3. Predominant Vbeta families were analysed by DNA sequencing to identify identical clones. Immunohistochemical staining of Vbeta families was performed to study the distribution of T cells expressing identified predominant Vbeta families. The muscle-infiltrating lymphocytes showed restricted expression of TCR Vbeta families. DNA sequencing proved that clonally expanded T cells were identical in different muscles and persisted 9 years after the first biopsy. Immunohistochemical analysis with Vbeta family-specific antibodies demonstrated the endomysial localization of these T cells in inflammatory cell infiltrates. Our results show that in IBM there is clonal restriction of TCR expression in muscle-infiltrating lymphocytes. Identical T-cell clones predominate in different muscles, and these clones persist for many years. These results indicate an important, continuous, antigen-driven inflammatory reaction in IBM.

Aged↗

PubMed2000

Transformation of Medicago truncatula via infiltration of seedlings or flowering plants with Agrobacterium.

Two rapid and simple in planta transformation methods have been developed for the model legume Medicago truncatula. The first approach is based on a method developed for transformation of Arabidopsis thaliana and involves infiltration of flowering plants with a suspension of Agrobacterium. The second method involves infiltration of young seedlings with Agrobacterium. In both cases a proportion of the progeny of the infiltrated plants is transformed. The transformation frequency ranges from 4.7 to 76% for the flower infiltration method, and from 2.9 to 27.6% for the seedling infiltration method. Both procedures resulted in a mixture of independent transformants and sibling transformants. The transformants were genetically stable, and analysis of the T2 generation indicates that the transgenes are inherited in a Mendelian fashion. These transformation systems will increase the utility of M. truncatula as a model system and enable large-scale insertional mutagenesis. T-DNA tagging and the many adaptations of this approach provide a wide range of opportunities for the analysis of the unique aspects of legumes.

Blotting, Southern↗

PubMed2002

Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice.

BACKGROUND: Urinary tract obstruction during development leads to tubular atrophy and causes interstitial fibrosis. Macrophage infiltration into the interstitium plays a central role in this process. Selectins, a family of three adhesion molecules, are involved in leukocyte recruitment to sites of inflammation and immune activity. We investigated the role of selectins in obstructive nephropathy in newborn mice. METHODS: Triple selectin-deficient mice (EPL-/-), L-selectin deficient mice (L-/-) and wild type mice (WT) were subjected to complete unilateral ureteral obstruction (UUO) or sham operation within the first 48 hours of life, and were sacrificed 5 and 12 days later. Kidneys were removed, and sections were stained for macrophage infiltration (mAb F4/80), apoptosis (TUNEL), tubular atrophy (periodic acid-Schiff) and interstitial fibrosis (Masson trichrome). RESULTS: Selectin deficient mice showed a marked reduction in macrophage infiltration into the obstructed kidney compared to WT at day 5 and day 12 after UUO. Tubular apoptosis was strongly reduced in EPL-/- at day 5 after UUO, and in EPL-/- and L-/- at day 12 after UUO when compared to WT. The number of apoptotic tubular cells was correlated with macrophage infiltration, suggesting that macrophages stimulate tubular apoptosis in obstructive nephropathy. In addition, tubular atrophy and interstitial fibrosis were significantly diminished in EPL-/- and L-/- compared to WT at day 12 after UUO. CONCLUSION: Following UUO, selectins mediate macrophage infiltration into the obstructed kidney, which in turn may induce tubular apoptosis, tubular atrophy and interstitial fibrosis.

Animals↗

PubMed2003

Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after severe warm ischemia/reperfusion renal injury.

BACKGROUND: Post-ischemia/reperfusion (I/R) damage, accompanied by leukocyte infiltration, is unavoidable in renal transplantation, as is the need for immunosuppressive treatment. Influence of immunosuppressive treatment on post-I/R renal damage, nonalloimmune cellular infiltration, and regeneration is not well studied. METHODS: Uninephrectomized inbred LEW rats were submitted to warm renal ischemia of 45 minutes/60 minutes, and received different immunosuppressive regimens: cyclosporine (CsA) 10 mg/kg/day subcutaneously in the neck daily, or mycophenolate mofetil (MMF) 20 mg/kg/day by daily oral gavage. Control animals underwent sham operation (unilateral nephrectomy) with immunosuppressive treatment or ischemia with vehicle administration. In addition the effect of MMF/mycophenolic acid (MPA) on renal tubule cell proliferation in culture was studied with bromodeoxyuridine incorporation. RESULTS: The post-I/R interstitial cellular infiltration/proliferation consisted mainly of mononuclear leukocytes [first monocytes/macrophages (Mo/MPhi) followed by CD4+ cells]. This mononuclear cell infiltration became apparent 24 hours after injury at the time of acute tubular necrosis, and was most prominent during the phase of regeneration. Severe I/R combined with CsA aggravated morphologic damage and dysfunction, without effect on tubular cell proliferation and tubular regeneration. Early leukocyte infiltration was qualitatively and quantitatively comparable to control animals, yet decreased moderately later in time. In contrast, MMF in combination with severe I/R did not influence initial morphologic damage and dysfunction. Although the initial leukocyte infiltration was comparable to control animals, the subsequent mononuclear cell accumulation, especially CD4 T cells decreased dramatically during MMF treatment. This was concomitant with a decrease of tubular cell proliferation and hence tubular regeneration. Increasing MPA concentrations in renal tubular cell culture caused a significant decrease in total cell number, and an almost arrest of bromodeoxyuridine incorporation, as measurement of cell proliferation. CONCLUSION: Immunosuppressive treatment with CsA or MMF affected significantly and in a different manner post-I/R renal morphologic damage, interstitial leukocyte, accumulation and regeneration.

Animals↗