bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opsonizing antibodies (IgG1) up-regulate monocyte proinflammatory cytokines tumour necrosis factor-alpha (TNF-α) and IL-6 but not anti-inflammatory cytokine IL-10 in mycobacterial antigen-stimulated monocytes—implications for pathogenesis
Authors: Hussain R , Shiratsuchi H , Phillips M , Ellner J , Wallis R S 
Published: March 2003

SUMMARYCachexia is one of the prominent features of advanced tuberculosis (TB) seen in association with increased expression of the monokine TNF-α. Several mycobacterial proteins, including PPD, stimulate TNF-α secretion from monocytes. Host factors that may play a role in cytokine expression from monocytes remain largely unknown. One such factor is the opsonizing antibodies. Monocytes have high-affinity receptors (FcγI and FcγIII) for IgG1 and IgG3 antibodies that mediate antigen uptake. We have reported selective up-regulation of IgG1 (which bind to Fcγ receptors) in advanced TB and have recently shown the ability of PPD-specific IgG1 antibodies to augment TNF-α expression in PPD-stimulated monocytes. These observations have now been extended to other cytokines with semipurified fractions from secreted antigens of Mycobacterium tuberculosis (containing 30 kD and 58 kD) that were devoid of lipids, glycolipids and carbohydrates. In the presence of heat-inactivated TB plasma containing known amounts of antigen-specific IgG1 antibodies, these fractions induced significantly increased TNF-α, IL-6 and IL-10 secretion. Absorption of IgG1 with Protein ‘A’ removed the augmenting activity for TNF-α and IL-6 secretion from the TB plasma samples. In the case of IL-10, removal of IgG1 resulted in increased rather than decreased IL-10 secretion. These results suggest a possible pathogenic role for antibodies in TB by enhancing proinflammatory and blocking down-regulatory cytokines such as IL-10 cytokines during the chronic phase of TB.
FTS reduces bleomycin-induced cytokine and chemokine production and inhibits pulmonary fibrosis in mice
Authors: Yara S , Kawakami K , Kudeken N , Tohyama M , Teruya K , Chinen T , Awaya A , Saito A 
Published: March 2003

SUMMARYBleomycin (BLM), an antitumour drug, is known to cause interstitial pneumonia followed by pulmonary fibrosis, and has often been used to produce an animal model of pulmonary fibrosis. In the present study, we examined the effect of a nonapeptide thymic hormone, facteur thymique serique (FTS), on the murine lung fibrosis induced by intratracheal instillation of BLM. Treatment with FTS ameliorated BLM-induced fibrotic changes in a dose-dependent manner, as indicated by the reduced accumulation of hydroxyproline (HP). In addition, FTS suppressed BLM-induced cellular inflammatory response in the lungs, as evidenced by inhibition of increased lung weight, reduced accumulation of inflammatory leucocytes, including lymphocytes and neutrophils, but not macrophages, and less pronounced histopathological changes. Finally, BLM challenge increased the local synthesis of proinflammatory cytokines, TNF-α and IL-1β and chemokines, MCP-1, MIP-1α RANTES, MIP-2 and KC, while administration of FTS suppressed the production of these cytokines, except for MCP-1. These effects of FTS were observed only when mice received intratracheal instillation with BLM. Considered collectively, our results indicated that FTS treatment ameliorated the cellular inflammatory responses and fibrotic changes in the lungs caused by BLM and such inhibition was well correlated with reduced synthesis of several fibrosis-related cytokines, and suggested that FTS may be potentially useful for the treatment of pulmonary fibrosis.
Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum
Authors: Ronkainen M S , Hämäläinen A -M , Koskela P , Åkerblom H K , Knip M 
Published: March 2003

SUMMARYTo evaluate whether pregnancy has any effect on insulin antibody levels and to test the concordance between a conventional radioimmunoassay and a new microassay for the detection of insulin antibodies, insulin antibodies were analysed in 104 mothers in early pregnancy and at delivery and in their newborn infants. Thirty-eight of the mothers had type 1 diabetes. The concordance between the assays was high in the samples taken in early pregnancy (95%), but substantially lower in the samples taken at delivery (40%) and in the cord blood samples (68%). A considerable proportion of the mothers at delivery, especially the unaffected mothers (71%), and the newborn infants of the unaffected mothers (32%) were positive for insulin antibodies in the conventional assay but not in the microassay. Insulin antibody levels increased in the mothers, significantly so in the unaffected mothers (P &lt; 0.001), during pregnancy in the conventional assay, whereas in the microassay they decreased significantly (P &lt; 0.01) in affected mothers and remained negative in the unaffected mothers. Since immune complexes are precipitated with protein A specific for IgG in the microassay and with polyethylene glycol lacking specificity for immunoglobulins in the conventional assay, our data indicate that insulin antibody levels decrease on average during pregnancy and that the increasing non-IgG anti-insulin activity observed in the conventional assay is induced by pregnancy and is present in both the maternal and the foetal circulation.
Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis
Authors: Fuse K , Kodama M , Hanawa H , Okura Y , Ito M , Shiono T , Maruyama S , Hirono S , Kato K , Watanabe K , Aizawa Y 
Published: March 2003

SUMMARYMonocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family that has been shown to play a major role in the migration of monocytes and T cells to an inflammatory focus. To clarify the role of MCP-1 in the pathogenesis of myocarditis, we have examined the expression of MCP-1 in rat hearts with experimental autoimmune myocarditis (EAM), and have also measured serum levels of MCP-1 in patients with histology-proven acute myocarditis. Lewis rats were immunized with cardiac myosin and were killed 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42 and 56 days after immunization. Large mononuclear cells in the myocardial interstitium were stained with an anti-MCP-1 antibody. mRNA of MCP-1 increased in the hearts of EAM rats from days 15–27 as shown by quantitative reverse transcription-polymerase chain reaction. Serum MCP-1 levels of the rats with EAM were significantly elevated from days 15–24. In the clinical study, serum levels of MCP-1 in 24 patients with acute myocarditis at the time of admission (165·2 ± 55·8 pg/ml) were significantly (P = 0·0301) elevated compared with those of 20 healthy volunteers (61·8 ± 10·7 pg/ml). Serum MCP-1 levels of 8 fatal cases (371·8 ± 145·2 pg/ml) were significantly (P = 0·0058) higher than those of 16 cases who survived (65·5 ± 12·8 pg/ml). In conclusions, MCP-1 may play an important role in the pathogenesis of human acute myocarditis as well as in the progression of rat EAM.
Differential responsiveness of cord and adult blood monocytes to hepatocyte growth factor
Authors: Jiang Q I , Azuma E , Tanaka M , Kobayashi M , Hirayama M , Kumamoto T , Iwamoto S , Yamamoto H , Nakashima K , Sakurai M , Komada Y 
Published: March 2003

SummaryMonocytes as antigen-presenting cells play an important role in host defence. There are several cytokines affecting monocyte function. We demonstrate that both adult and cord blood monocytes constitutively express hepatocyte growth factor (HGF) receptor, MET. HGF significantly down-regulated MET expression of adult blood monocytes, compared with cord blood monocytes, when cultured either in RPMI-1640 containing 10% FBS or serum-free medium. Surface levels of MET correlated with c-met mRNA levels both in adult and cord blood when cultured. MET expression was down-regulated by treating with actinomycin D or cycloheximide. HGF stimulated DNA synthesis of adult monocytes, but not cord blood. HGF enhanced antigen-presenting capacity of adult blood monocytes but not cord blood monocytes. HGF up-regulated HLA class I expression in adult monocytes but not in cord blood monocytes. The current results suggest that the failure of cord blood monocytes to respond to HGF may be responsible, in large part, for their functional immaturity.
Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia
Authors: Orleans-Lindsay J K , Barber L D , Prentice H G , Lowdell M W 
Published: March 2003

SummaryEvidence of an immune mediated graft-versus-leukaemia effect has led to the belief that T and NK cell based adoptive immunotherapy can constitute effective treatment for relapsed leukaemias. However, work on solid tumours has shown this strategy may be hampered, by an immune escape mechanism in which tumour secreted immunosuppressive factors compromise T and NK cell function. Indeed, acute myeloid leukaemia (AML) cells secrete immunosuppressive factors that block the synthesis of Th1 type cytokines in T cells. We demonstrate here that this immunosuppression, mediated by both HL60 AML cell line and primary AML blasts, inhibits T and NK cell proliferation but not cytolytic activity.Supernatants from HL60 cell line and primary AML blasts inhibited T cell proliferation to mitogenic and alloantigen stimulation but had no effect on cytolytic function. Similarly, the proliferation of NK cells to IL-2 and IL-15 stimulation was inhibited whilst their cytolytic function, shown by lysis of AML blasts, K562 and Daudi cells remained unaffected. The failure of T and NK cells to proliferate was not due to effector cell apoptosis. Indeed, removal of lymphocytes from the immunosuppressive environment partially restored their capacity to respond to mitogenic stimulation. T cells exposed to immunosuppressive supernatants did not increase expression of mitotic inhibitory proteins that arrest cell division, thereby ruling this out as a mechanism of operation for this immunosuppression. T cell expansion requires antigen stimulation, usually provided in the form of AML blasts, therefore our data suggest that NK cells may be more practical for the immunotherapy of AML.
The influence of diesel exhaust particles on mononuclear phagocytic cell-derived cytokines: IL-10, TGF-βand IL-1β
Authors: Pacheco K A , Tarkowski M , Sterritt C , Negri J , Rosenwasser L J , Borish L 
Published: March 2003

SummaryDiesel exhaust particles (DEP) are known to modulate the production of cytokines associated with acute and chronic respiratory symptoms and allergic respiratory disease. Tolerance is an important mechanism through which the immune system can maintain nonresponsiveness to common environmental antigens. We examined the effect of DEP on IL-10 and TGF-β, cytokines produced by macrophages and repressor (Tr-like) lymphocytes which influence tolerance. Human PBMCs (n = 22) were incubated with 1–100 ng/ml of DEP, and suboptimally primed with LPS. IL-10 gene expression was assessed by the S1 nuclease protection assay, and production of IL-10, TGF-β, TNF-α, IL-1β and IL-4 stimulated CD23 was evaluated by ELISA after 24 and 48 h. The effect of the order of exposure to DEP and LPS was evaluated on IL-10 protein and mRNA in cells (1) preincubated with LPS followed by DEP, or (2) exposed first to DEP followed by LPS. IL-10 was further evaluated using benzo[a]pyrene and [α]naphthoflavone as a surrogate for the polyaromatic hydrocarbons (PAHs) adsorbed to DEP. Control cells were incubated with carbon black, without PAHs. In PBMCs exposed to DEP with LPS, or preincubated with LPS before DEP, IL-10 production and mRNA fall significantly. TGF-β is similarly suppressed, IL-1β secretion is significantly stimulated, and IL-4 stimulated CD23 release rises in the atopic subjects. In contrast, when DEP is added prior to LPS, IL-10 production rises, and IL-1β falls to zero. These effects on IL-10 are reproduced with benzo[a]pyrene and reversed by the coaddition of [α]naphthoflavone, its known antagonist. The carbon black fraction has no effect on IL-10 production. The effect of DEP on IL-10 can be inhibitory or stimulatory, depending on the order of exposure to DEP and LPS. Pro-inflammatory cytokines and factors rise when IL-10 is inhibited, and are suppressed when IL-10 is stimulated. These results are duplicated with benzo[a]pyrene, suggesting that the PAH portion of the DEP is the active agent.
Th2 dominance in nasal mucosa in patients with Wegener’s granulomatosis
Authors: Balding C E J , Howie A J , Drake-Lee A B , Savage C O S 
Published: March 2003

SummaryWegener's granulomatosis initially affects upper respiratory tract organs including the nasal mucosa in more than 90% of patients. The inflammation is typically granulomatous with associated vasculitis. T lymphocytes are usually a prominent component of the leucocyte infiltrate. Previous studies using peripheral blood T cells have implicated IFN-γ rich Th1-type responses. This study addressed the cytokine milieu in nasal mucosa from 10 patients with active Wegener's granulomatosis using immunohistochemistry. Increased levels of CD3+ T cells and eosinophils were present compared with normal and disease controls. There was increased expression of IL-4, down-regulation of IL-2 and no detectable IFN-γ. There was increased expression of the chemokine receptor CCR3 by infiltrating cells, consistent with an IL-4 dominant, Th2-biased response. In contrast, renal biopsy tissue from 10 patients with active Wegener's granulomatosis showed expression of IL-2 and IL-4. The Th2-type environment within nasal mucosa, often the initial site of disease activity in Wegener's, is consistent with a local allergic response in these patients.
Prostaglandin E2 down-regulates viable Bacille Calmette–Guérin-induced macrophage cytotoxicity against murine bladder cancer cell MBT-2in vitro
Authors: YAMADA H , KURODA E , MATSUMOTO S , MATSUMOTO T , YAMADA T , YAMASHITA U 
Published: March 2003

SUMMARYThe regulatory effect of prostaglandin (PG) E2 and a cyclooxygenase (COX) inhibitor on Bacille Calmette–Guérin (BCG)-induced macrophage cytotoxicity in a bladder cancer cell, MBT-2, was studied in vitro. BCG stimulated thioglycollate-elicited murine peritoneal exudate cells (PEC) to induce cytotoxic activity and to produce cytokines such as interferon (IFN)-γ, tumour necrosis factor (TNF)-α and PGE2. NS398, a specific COX-2 inhibitor, and indomethacin (IM), a COX-1 and COX-2 inhibitor, enhanced viable BCG-induced cytotoxic activity and IFN-γ and TNF-α production of PEC. However, NS398 and IM did not enhance these activities induced by killed BCG. Enhanced cytotoxicity was mediated by increased amounts of IFN-γ and TNF-α. Exogenous PGE2 reduced cytotoxic activity and IFN-γ and TNF-α production of PEC. These results suggest that PGE2 produced by BCG-activated macrophages has a negative regulatory effect on the cytotoxic activity of macrophages. Accordingly, a PG synthesis inhibitor may be a useful agent to enhance BCG-induced antitumour activity of macrophages.
Treatment with methylprednisolone in relapses of multiple sclerosis patients: immunological evidence of immediate and short-term but not long-lasting effects
Authors: Martínez-Cáceres E M , Barrau M A , Brieva L , Espejo C , Barberà N , Montalban X 
Published: March 2003

SummaryRelapses of multiple sclerosis (MS) are treated commonly with high-dose intravenous methylprednisolone (MP) given over a period of 3–5 days. The mechanisms responsible for the beneficial effects of MP in attacks are not clearly established. It is also controversial whether this treatment may have a long-term effect. Here, peripheral blood samples from relapsing–remitting MS patients in acute relapse were analysed by flow cytometry just before steroid treatment and at different time points after initiation of the therapy. We observed an immediate (day 3) decrease in the percentage of CD4+ lymphocytes, with a relative increase in the memory (CD4+CD45R0+) subpopulation. A longer standing effect of MP on IFN-γ production, CD54, CCR5, CXCR3 and CD95 (Fas) expression was also observed on CD4+ cells after 1 month of treatment initiation. Six months after the therapy, during clinical remission, no changes due to ivMP therapy were detected. These results support that MP treatment of relapses induces immediate post-treatment and short-term effects on the immune system that could partly account for the clinical and radiological improvement observed in MS patients. However, no conclussion can be drawn as to a possible long-term or even intermediate influence of ivMP treatment on the course of the disease.
Defining a T-cell epitope within HSP 65 in recurrent aphthous stomatitis
Authors: HASAN A , SHINNICK T , MIZUSHIMA Y , VAN DER ZEE R , LEHNER T 
Published: March 2003

SUMMARYThe 65 kD heat shock protein (HSP) has been implicated in the aetiology of recurrent aphthous stomatitis (RAS). We have previously demonstrated that peptide 91–105 derived from the sequence of mycobacterial 65 kD HSP stimulates specifically lymphocytes from patients with RAS. In this investigation, we show that both CD4+ and CD8+ T cells were significantly stimulated with mycobacterial peptide 91–105. In contrast, the human homologous peptide 116–130 stimulated only CD4+ T cells. Inhibition studies showed that CD4+ T cells were class II restricted, whereas CD8+ T cells were class I restricted. We then used truncated or substituted peptides, and demonstrated that residues 95–105 appear to be important, and residue 104(Arg) critical, in stimulating the T cells. Thus, peptide 95– 105 may constitute a T-cell proliferative epitope in RAS. We postulate that the high load of micro-organisms that colonize the oral mucosa may initiate an immune response by the microbial HSP 65-derived peptide 95–105, stimulating the numerous Langerhans cells in the oral mucosa to activate a cross-reacting immune response to the homologous peptide 116–130 within the epithelial HSP 60, initiating the immunopathological changes that lead to RAS.
Caspase activation in the absence of mitochondrial changes in granulocyte apoptosis
Authors: NOPP A , LUNDAHL J , STRIDH H 
Published: March 2003

SUMMARYEosinophils and neutrophils are two different types of granulocytes evolved from a common haematopoetic precursor in the bone marrow. Eosinophils are mainly involved in parasitic infection and allergic inflammation while neutrophils mainly participate in the defence against bacterial infections. Prolongation of granulocyte life span by inhibition of apoptosis may lead to tissue load of cells, and this has been detected in different inflammatory reactions. The molecular mechanisms and the potential role of the mitochondria in granulocyte apoptosis are poorly understood. In the present study we have characterized further the role of the mitochondria in granulocyte-apoptosis by studying the sequence of mitochondrial permeability transition (MPT) induction, loss of mitochondrial membrane potential (Δψm) and release of cytochrome c. This was made possible by applying tributyltin (TBT), a well-characterized apoptotic stimulus and MPT-inducer. We also studied potential differences in apoptosis-susceptibility between eosinophils and neutrophils. Ten minutes of TBT-exposure resulted in a substantial caspase-3 activity in both eosinophils and neutrophils, followed by phosphatidylserine (PS)-exposure after 30–120 min. Interestingly, caspase-3 activity was not preceded by MPT-induction, loss of Δψm or by cytochrome c-release in either eosinophils or neutrophils. In conclusion, we have demonstrated an extremely rapid induction of caspase-3 activity and apoptosis in human blood granulocytes without prior mitochondrial changes, including loss of mitochondrial membrane potential and release of cytochrome c. Our results open the possibility for a mitochondrial-independent activation of caspase 3 and subsequent apoptosis in granulocytes.
Suppression of autologous peripheral blood mononuclear cell proliferation by alveolar macrophages from young infants
Authors: BUNN H J , HEWITT C R A , GRIGG J 
Published: March 2003

SUMMARYMaintenance of lung homeostasis involves a complex interaction between T lymphocytes and alveolar macrophages (AM), in which AM suppress pulmonary T cell proliferation to antigenic stimuli. To assess whether AM-mediated suppression is attenuated in healthy young infants, AM and peripheral blood mononuclear cells (PBMC) were sampled prior to elective surgery. Children were divided into &lt;4 months of age (Group I) and &gt;4 months (Group II). Autologous PBMC and AM were co-cultured in vitro with phytohaemaglutinin (PHA) at AM : PBMC ratios ranging from 2:1 to 1 : 5. Methyl-tritiated thymidine was added after 48 h and uptake determined at 72 h. Percentage suppression or enhancement of PBMC proliferation by AM was determined relative to proliferation of PBMC with PHA. To determine the role of soluble factors of suppression, cell-free supernatants from paediatric AM and PBMC co-cultures were added to PHA-stimulated adult PBMC. The median age was 3 months for Group I (n = 9) and 7 years 2 months (n = 13) for Group II. Percentage suppression of PBMC proliferation was attenuated in Group I (versus Group II) at AM : PBMC ratios of 2:1 (median 78%versus 92%, P &lt; 0·05) and 1 : 1 (45%versus 87%, P &lt; 0·01). Cell-free supernatants from Groups I and II suppressed proliferation of adult PBMC, but there was no difference in suppression between the age groups. We conclude that suppression of autologous PHA-stimulated PBMC proliferation by AM is attenuated in young infants, and this immaturity is not explained by reduced release of soluble factors.
Effect of arsenic, cadmium and lead on the induction of apoptosis of normal human mononuclear cells
Authors: DE LA FUENTE H , PORTALES-PÉREZ D , BARANDA L , DÍAZ-BARRIGA F , SAAVEDRA-ALANÍS V , LAYSECA E , GONZÁLEZ-AMARO R 
Published: March 2003

SUMMARYThe aim of this work was to investigate the effect of cadmium, lead and arsenic on the apoptosis of human immune cells. Peripheral blood mononuclear cells (MNC) were incubated with increasing concentrations of these metals and then cellular apoptosis was determined by flow cytometry and by DNA electrophoresis. We found that arsenic induced a significant level of apoptosis at 15 μm after 48h of incubation. Cadmium had a similar effect, but at higher concentrations (65 μm). In addition, cadmium exerted a cytotoxic effect on MNC that seemed to be independent of the induction of apoptosis. In contrast, concentrations of lead as high as 500 μm were nontoxic and did not induce a significant degree of apoptosis. Additional experiments showed that arsenic at concentrations as low as 1·0 μm had a significant pro-apoptotic effect when cells were cultured in the presence of this pollutant for more than 72 . Non-T cells were more susceptible than T lymphocytes to the effect of arsenic and cadmium. Interestingly, MNC from children chronically exposed to arsenic showed a high basal rate of apoptosis and a diminished in vitro sensibility to this metalloid. Our results indicate that both arsenic and cadmium are able to induce apoptosis of lymphoid cells, and suggest that this phenomenon may contribute to their immunotoxic effect in vivo.