Biomedical subjects

M Reale

Publications and source records attributed to M Reale.

At least 19 recordsLinked to original sources

PubMed2003

Oxygen supply modulates MCP-1 release in monocytes from young and aged rats: decrease of MCP-1 transcription and translation is age-related.

Hyper or hypoxia may affect the immune system's chemokine production. Monocyte chemotactic protein-1 (MCP-1), an important chemotactic cytokine can be activated by active oxygen species. Groups of rats were exposed to hypoxic and hyperoxic environmental conditions for 60 h and MCP-1 was determined in their peripheral blood mononuclear cells by Elisa and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). In this study we evaluated if the ability of monocytes to produce MCP-1 under basal conditions or after stimulation with lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) was differently affected by exposure to hyper or hypoxic conditions in young and aged rats. MCP-1 expression and production in monocyte/macrophages from rats at normoxic conditions was reduced in aged subjects. However, spontaneous, LPS or PHA-induced MCP-1 production was up-regulated by exposure to hyperoxic conditions in both young (62 +/- 8, 99 +/- 7, 102 +/- 8 pg/ml, respectively) and aged rats (79 +/- 4, 112 +/- 9, 117 +/- 10 pg/ ml, respectively). We conclude that hyperoxia is an important regulator of MCP-1 release and support the hypothesis that increased % of O2 may serve to initiate MCP-1 production which then serves to recruit and regulate the distribution of mononuclear cells to the sites of inflammation.

Aging↗

PubMed2001

Effects of electromagnetic fields produced by radiotelevision broadcasting stations on the immune system of women.

The object of this study was to investigate the immune system of 19 women with a mean age of 35 years, for at least 2 years (mean = 13 years) exposed to electromagnetic fields (ELMFs) induced by radiotelevision broadcasting stations in their residential area. In September 1999, the ELMFs (with range 500 KHz-3 GHz) in the balconies of the homes of the women were (mean +/- S.D.) 4.3 +/- 1.4 V/m. Forty-seven women of similar age, smoking habits and atopy composed the control group, with a nearby resident ELMF exposure of < 1.8 V/m. Blood lead and urinary trans-trans muconic acid (a metabolite of benzene), markers of exposure to urban traffic, were higher in the control women. The ELMF exposed group showed a statistically significant reduction of blood NK CD16+-CD56+, cytotoxic CD3(-)-CD8+, B and NK activated CD3(-)-HLA-DR+ and CD3(-)-CD25+ lymphocytes. 'In vitro' production of IL-2 and interferon-gamma (INF-gamma) by peripheral blood mononuclear cells (PBMC) of the ELMF exposed group, incubated either with or without phytohaemoagglutinin (PHA), was significantly lower; the 'in vitro' production of IL-2 was significantly correlated with blood CD16+-CD56+ lymphocytes. The stimulation index (S.I.) of blastogenesis (ratio between cell proliferation with and without PHA) of PBMC of ELMF exposed women was lower than that of the control subjects. The S.I. of blastogenesis of the ELMF exposed group (but not blood NK lymphocytes and the 'in vitro' production of IL-2 and INF-gamma by PBMC) was significantly correlated with the ELMF levels. Blood lead and urinary trans-trans muconic acid were barely correlated with immune parameters: the urinary metabolite of benzene of the control group was only correlated with CD16+-CD56+ cells indicating a slight effect of traffic on the immune system. In conclusion, this study demonstrates that high frequency ELMFs reduce cytotoxic activity in the peripheral blood of women without a dose-response effect.

Adult↗

PubMed2001

Effects of low frequency electromagnetic fields on expression of lymphocyte subsets and production of cytokines of men and women employed in a museum.

The objective of this study was to analyse the immune response to electromagnetic fields (ELMFs) in seven men and eight women employed in a museum. The workers were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39 men with a similar percentage of atopic subjects, age (range 30-51 years) and smoking habits of the workers included in the study. Levels of blood lead (Pb) and urinary trans-trans muconic acid, a metabolite of benzene (markers of exposure to traffic and smoking) of the control and exposed groups were similar. Lymphocyte subsets were determined in men and women using conjugated antibodies. Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA), as well as blastogenesis of PMBCs induced by PHA, were determined in women only. ELMF-exposed women showed a significant reduction in the percentage of B and NK CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes. They also showed significantly lower levels of interferon gamma in serum, or produced in the supernatants by PMBCs both spontaneously and stimulated by PHA, while they did not show significant changes in serum and 'in vitro' produced IL-4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to the controls, a statistically significant reduction in both number and percentage of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this investigation demonstrates a reduction of blood NK lymphocytes and of the production of interferon gamma in workers exposed to low frequency ELMFs. Recent studies have shown that stress and poor lifestyle induce the reduction of blood cytotoxic activities possibly acting on nervous functions. This may suggest that ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous systems.

Adult↗

PubMed2001

Differential expression and secretion of RANTES and MCP-1 in activated peripheral blood mononuclear cell cultures of atopic subjects.

RANTES and MCP-1 represent a link between the activation of monocytes, lymphocytes, basophils, mast cells and eosinophils in inflammatory disorders, such as the late phase allergic reaction. These C-C chemokines also play a role in regulating Th cell cytokine production and leukocyte trafficking. In this study, we determined the expression and secretion of RANTES and MCP-1 from PHA-activated PBMC of healthy and atopic subjects with no symptoms. Levels of RANTES from PHA-activated PBMC of atopic patients were higher, at 18 and 24 h incubations (42+/-5.5 and 48+/-4), compared to controls (20+/-4 and 35+/-4), respectively; while MCP-1 was not (12+/-3 and 17+/-3) compared to controls (10.5+/-3 and 15+/-2), respectively. This effect was also revealed on RANTES mRNA expression, as determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, PHA-activated PBMC of atopic subjects produce more IL-4 (five times more) than healthy subjects, while IFN-gamma did not vary. RANTES, compared to MCP-1, may have more influence on signal transduction pathways, either in physiologic or inflammatory states and may induce profound effects on the regulation of cell activity. The differential production of RANTES and MCP-1 may lead to diverse regulation of the function and development of cells involved in the allergic response. These studies emphasize the importance of chemokine selectivity during inflammation.

Cells, Cultured↗

PubMed2001

Involvement of phosphatidylserine exposure in the recognition and phagocytosis of uremic erythrocytes.

Cell surface-exposed phosphatidylserine (PS) represents a signal for macrophage recognition and cell phagocytosis. This study examines PS exposure and susceptibility to erythrocyte phagocytosis in patients with chronic uremia in an attempt to assess the possible pathogenic mechanism behind cell removal in a condition associated with shortened erythrocyte life. Both PS-expressing erythrocytes and erythrophagocytosis (human monocyte-derived macrophages ingesting one or more erythrocytes) were significantly increased in uremic patients compared with healthy controls. Phagocytosed uremic erythrocytes appeared intact, suggesting they were identified before lysis through some surface change recognized by the macrophages. The degree of phagocytosis was markedly greater for PS-positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic erythrocytes. A significant correlation (r = 0.655) was found between the percentage of PS-expressing red blood cells (RBCs) and the percentage of phagocytosing macrophages in uremic patients. Reconstitution experiments showed the ability of uremic plasma to promote both PS exposure and erythrophagocytosis, the latter without direct interaction with the macrophage population. Phagocytosis of uremic erythrocytes was strongly inhibited when the macrophages were preincubated with glycerophosphorylserine (GPS), a structural derivative of PS, but this was not the case with the equivalent derivative of phosphatidylethanolamine, glycerophosphorylethanolamine. This inhibition appeared to be specific because GPS failed to inhibit the phagocytosis of opsonized uremic erythrocytes that occurs through an Fc receptor-mediated pathway. These findings suggest that a PS-recognition mechanism may promote the susceptibility of uremic RBCs to phagocytosis and thus be involved in the shortened erythrocyte life span of uremia.

Anemia↗

PubMed2001

Immunohistochemical analysis of Ki-67, p21waf1/cip1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial.

OBJECTIVE: To investigate Ki-67 and p21Waf1/Cip1 expression and apoptosis, before and after treatment, in tumour biopsies obtained from patients with superficial bladder cancer who underwent vinorelbine intravesical therapy. PATIENTS AND METHODS: Twenty patients with high-risk superficial bladder cancer (including one or more of the following parameters: tumour diameter > 3 cm, histological grade 3, or multicentric tumours) were treated 1-6 times (weekly) with intravesical vinorelbine (50 mg/mL) instillations. Transurethral tumour marker biopsies were obtained one week before the first instillation of the drug and one week after the last. The biopsies were immunostained for Ki-67 and p21Waf1/Cip1 with monoclonal antibodies, on tissue sections derived from paraffin-embedded samples obtained before and after vinorelbine treatments. In addition, apoptosis was determined using a terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labelling (TUNEL) technique. RESULTS: There were no significant differences in the cell proliferation marker Ki-67 in biopsies taken before or after treatment. However, p21Waf1/Cip1 showed significantly higher expression in biopsies obtained after vinorelbine treatment, with median (range) values of 40 (20-90)% before and 70 (50-80)% after (P < 0.001, paired nonparametric Wilcoxon test). The apoptotic index was significantly higher after vinorelbine therapy, with median (range) values of 0.89 (0.06-3.8)% before and 2.25 (0.17-18.7)% after treatment (P < 0.001, paired nonparametric Wilcoxon test). Despite the brief treatment and few patients there was a clinical response in nine patients, together with low toxicity in all. CONCLUSION: The intravesical treatment of tumours with vinorelbine affects p21Waf1/Cip1 expression without blocking cell proliferation, although increasing apoptosis. The preliminary results suggest that vinorelbine may be useful for treating superficial bladder tumours, and thus a phase II study is warranted.

Administration, Intravesical↗

PubMed2001

Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with pancreatic cancer.

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty.

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis that MCP-1 exerts its effect, at least in part, by inducing O(2)(-) generation in circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had repeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, compared with nonrestenotic patients, had statistically significant (P<0.0001) elevated levels of MCP-1. In contrast, plasma levels of other chemokines, such as RANTES and interleukin-8, did not differ between the 2 groups after PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monocyte activity, as reflected by enhanced O(2)(-) generation. Finally, multivariate regression analysis showed that the MCP-1 plasma level measured 15 days after PTCA was the only statistically significant independent predictor of restenosis (beta=0.688, P<0.0001). This study suggests that MCP-1 production and macrophage accumulation in the balloon-injured vessel may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further understanding of the mechanism(s) by which MCP-1 is produced and acts after arterial injury may provide insight into therapies to limit the progression of atherosclerosis and restenosis after balloon angioplasty.

Aged↗

PubMed2001

Expression and secretion of RANTES by human peripheral blood CD4+ cells are dependent on the presence of monocytes.

The cDNA for RANTES (an acronym for "Regulated upon Activation, Normal T cell Expressed and Secreted") was initially discovered by subtractive hybridization as a T cell-specific sequence. Consistent with it being a C-C (beta) chemokine, RANTES is a monocyte chemoattractant. In addition, RANTES can chemoattract unstimulated CD4+/CD45RO+ memory T cells and stimulated CD4+ and CD8+ T cells with the naive and memory phenotypes in immunologically active sites. It has been shown that CD8+ cells are dominant sources of RANTES. Here we attempted to determine if CD4+ cells express and secrete RANTES alone, or if other accessory cells (activated monocytes) are needed to activate them. We found that when autologous monocytes are added to CD4+ cells and then stimulated with phytohaemagglutinin (PHA), the quantity of RANTES, in terms of transcription and translation of the protein, is significantly higher than the amount produced by the PHA-activated monocytes alone; isolated CD4+ cells stimulated with PHA do not produce any appreciable quantity of RANTES. When CD4+ cells are primed overnight with monocytes and then stimulated with PHA, they produce more RANTES compared to PHA-stimulated CD4+ cells alone. The influence that monocytes have on CD4+ cells to produce RANTES was confirmed when the physiological activator, tumor necrosis factor-alpha (TNF-alpha), was used. These data show that CD4+ cells need monocytes to express and secrete appreciable amounts of RANTES.

Blotting, Northern↗

PubMed2000

Endothelial NOS expression and ischemia-reperfusion in isolated working rat heart from hypoxic and hyperoxic conditions.

Induction of endothelial nitric oxide synthase (eNOS) contributes to the mechanism of heart protection against ischemia-reperfusion damage. We analyzed the effects of hypoxia and hyperoxia on eNOS expression in isolated working rat hearts after ischemia-reperfusion damage. Adult male Wistar rats were submitted to chronic hypoxia (2 weeks) and hyperoxia (72 h). The hearts were submitted to 15 min of ischemia and reperfused for 60 min, then we evaluated hemodynamic parameters and creatine phosphokinase (CPK) release. eNOS expression was estimated by RT-PCR; enzyme localization was evaluated by immunohistochemistry and the eNOS protein levels were detected by Western blot. All hemodynamic parameters in hypoxic conditions were better with respect to other groups. The CPK release was lower in hypoxic (P<0.01) than in normoxic and hyperoxic conditions. The eNOS deposition was significantly higher in the hypoxic group versus the normoxic or hyperoxic groups. The eNOS protein and mRNA levels were increased by hypoxia versus both other groups. Chronic hypoxic exposure may decrease injury and increase eNOS protein and mRNA levels in heart subjected to ischemia-reperfusion.

Animals↗

PubMed2000

Localization of the e-NOS enzyme in endothelial cells and odontoblasts of healthy human dental pulp.

Nitric oxide synthases (NOS) are important enzymes present in different cells such as endothelial cells, macrophages, etc. Recently, it has been found that nitric oxide (NO) is responsible for vasodilation, blood pressure regulation, platelet aggregation, cardiac contractility, and the mediation of immunity during bacterial infections and inflammation. However, the production and role of NO in various structures of the oral cavity have not been investigated extensively. The aim of this study was to evaluate the presence of e-NOS in healthy human odontoblasts and endothelial cells of the dental pulp. Twenty healthy human dental pulps were collected and frozen and pulp slices were obtained using a cryostat. The e-NOS enzyme was revealed by immunohistochemical analysis and the enzyme level was detected by Western blotting and mRNA expression by RT-PCR. The immunohistochemical results demonstrated, for the first time, the presence of e-NOS in odontoblasts and in endothelial cells. The presence of e-NOS m-RNA was confirmed by RT-PCR and the expression of the protein by Western blotting. These results clearly show that the e-NOS enzyme is present in both odontoblasts and endothelial cells of healthy human pulp. The presence of e-NOS in the odontoblast and endothelial cells of the dental pulp may mediate local vasodilation and cell proliferation.

Blotting, Western↗

PubMed2000

RANTES production and expression is reduced in relapsing-remitting multiple sclerosis patients treated with interferon-beta-1b.

RANTES (regulated upon activation, normal T-cell expressed and secreted), a CC chemokine, appears to play a role in the pathogenesis of relapsing-remitting multiple sclerosis (RR-MS), enhancing the inflammatory response within the nervous system. We have demonstrated that RANTES production is increased in RR-MS compared to controls. Interferon-beta-1b (IFN-beta-1b) treatment reduces RANTES production in sera and peripheral blood adherent mononuclear cell (PBAM) supernatants both in relapse and remission. IFN-beta-1b also reduces RANTES expression in PBAM. Our results suggest that RANTES modulation might represent one of the mechanisms of action of IFN-beta-1b in RR-MS.

Adjuvants, Immunologic↗

PubMed2000

Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic women exposed to an urban environment.

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.

Adult↗

PubMed1999

Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo.

Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. However, the exact role, function, and implication in inflammatory diseases remain to be determined. Here we report that subcutaneous injections (0.2 ml) of a saturated water solution (1:40) of potassium permanganate crystals induces the generation of granuloma tissue at the site of injection in the rat, and reaches its peak of formation after 1 week. The size and weight of the granulomas were increased by i.p. lipopolysaccharide (LPS) (6 microgram/200 microliter) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 300 microgram/200 microliter) treatments in rats, injected 18 hours before sacrifice. Moreover, steady-state levels of MCP-1 mRNA in the granuloma tissue (control), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-treated) whereas in animals treated with Dxs, there was a decrease in (P < 0.05) in formation of mRNA protein. When the granuloma tissues were homogenized the generation of MCP-1 was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in the Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples were further incubated in vitro with LPS (100 ng/ml) overnight. A Strong increase (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calcified tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dxs.

Animals↗

PubMed1999

Expression of lymphocyte subpopulations, cytokine serum levels, and blood and urinary trace elements in asymptomatic atopic men exposed to an urban environment.

The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.

Case-Control Studies↗

PubMed1999

Peripheral blood mononuclear cell production of interleukin-8 and IL-8-dependent neutrophil function in hypercholesterolemic patients.

Interleukin-8 is a cytokine produced by mononuclear cells that is involved in polymorphonuclear neutrophil leukocyte (PMN) recruitment and activation. Several studies have previously demonstrated a leukocyte activation during hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been found to play a role in the prevention of atherothrombotic disease. The purpose of this study was to determine interleukin-8 (IL-8) mRNA expression and ex vivo production from peripheral blood mononuclear cells (PBMCs) and IL-8-dependent PMN activation of hypercholesterolemic (HC) patients with respect to normocholesterolemic (NC) subjects. Using Northern blot analysis, we found a four- and threefold increase in the amount of IL-8 transcript in PBMC from HC patients, in unstimulated and LPS stimulated cultures, respectively. A specific immunoassay showed a correspondingly significant increase of IL-8 immunoactivity in the conditioned medium of PBMC from HC subjects as compared with controls (unstimulated PBMC: 15 +/- 4 vs. 4.2 +/- 3 ng/ml; P < 0.0001; LPS stimulated PBMC: 65.3 +/- 8 vs. 36.6 +/- 9 ng/ml; P < 0.0001). PMN of HC patients stimulated with IL-8 showed a reduced elastase release with respect to NC subjects before physiological granule release after f-Met-Leu-Phe (fMLP) treatment. These results indicate an upregulation of the IL-8 system in dyslipidemic patients and provide evidence for ongoing in vivo IL-8-dependent PMN activation during hypercholesterolemia.

Adult↗

PubMed1999

Systemic effects of ingested nickel on the immune system of nickel sensitised women.

This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women (group B) were non-symptomatic, while 7 Ni-sensitised women (group C) showed a flare up of urticaria and/or eczema. Serum and urine Ni were greatly lower before Ni administration than after 4 and 24 hours, without difference among the 3 groups. Before treatment, group B and C showed higher values of blood CD19+ and CD5--CD19+ cells than group A, while group C showed higher serum interleukin (IL) 2 and lower serum IL-5. Four hours after Ni ingestion, group C showed significant increase in serum IL-5. Twenty-four hours after treatment, group A showed a significant reduction in blood CD4+-CD45RO- "virgin" cells and an increase of CD8+ lymphocytes, while group C showed a marked decrease in total blood lymphocytes and CD3+, CD4+-CD45RO-, CD4+-CD45RO+, CD8+, CD19+ and CD5--CD19+ cell subsets. These data may be explained with migration of lymphocytes in tissues with a Th0-like immune response, as shown by the elevated serum IL-2 and the increase of serum IL-5 during the test.

Adolescent↗

PubMed1999

Effect of electromagnetic fields on several CD markers and transcription and expression of CD4.

We carried out flow cytometric analysis for multiparametric evaluation of cell surface markers related to cellular functions. Specifically, we studied the expression of CD4, CD8, CD3, CD16, CD19, HLA-DR, and CD14 macrophage receptors expression and cell cycle progression on cells exposed to ELF-EMF. In addition, we tested the effects of ELF-EMF on CD4 mRNA protein transcription and translation and the cell-cycle progression using an immunofluorescence method. Our data show that same CD surface marker expression are weakly influenced by electromagnetic fields, with no differences between cells exposed or not exposed to ELF-EMFs. However, when the CD4 protein generation was studied, an indication of protein production was found in lymphocytes exposed to ELF-EMF, as evidenced by immunofluorescence, Western blotting and RT-PCR analysis. CD16 and CD14 expression were affected by EMF exposure at all times studied (24, 48, 72 h). The results obtained with cell cycle analysis show that after 48 h of exposure to ELF-EMF, PHA-activated and not activated cells in S phase increase with respect to non-exposed cells. The findings from this study demonstrate that under our defined experimental conditions there is evidence that ELF-EMF has a slight effect on CD4, CD14 and CD16 receptor expression, while the other CD receptors are not affected.

Antigens, CD↗