Severe acute cerebrovascular disease revealing hepatitis C virus infection: effectiveness of alpha-interferon.
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Action Potentials↗
Biomedical subjects
G Ricevuti
Publications and source records attributed to G Ricevuti.
Inhibition of leukocyte and platelet aggregation in vitro by antithrombin.
Glycosaminoglycan-mediated aggregation of cells occurs through adhesion mechanisms in which heparan sulfate chains bind to counter receptors on these cells. As antithrombin interacts with heparan sulfate proteoglycans through its heparin-binding domain and inhibits leukocyte adhesion in ischaemia/reperfusion, it may affect leukocyte aggregation. Leukocyte aggregation was therefore monitored in vitro as the increase in transmission of light through stirred suspensions in a platelet aggregometer. Aggregation curves were quantified as the area under the curve in the first 6 min following stimulation. Leukocytes in platelet-rich plasma were obtained from heparinized whole blood of healthy donors by centrifugation; the ratio of leukocytes to platelets was about 1:45, and the final concentration of autologous plasma was 80%. Neutrophils were purified by dextran sedimentation, density centrifugation, and hypotonic lysis of erythrocytes. Aggregation was induced by phytohaemaglutinin (0.24 mg/mL) or formyl-Met-Leu-Phe (0.2 x 10(-6) M), with or without various concentrations of antithrombin. During the observation period (6 min) no aggregation of leukocytes in platelet-rich plasma or isolated neutrophils could be induced either with medium or with antithrombin (0.2 x 10(0) to 0.2 x 10(-6) IU/mL). Addition of phytohaemagglutinin or formyl-Met-Leu-Phe stimulated aggregation of leukocytes in platelet-rich plasma and neutrophils to different extents. Additional presence of anti-thrombin significantly inhibited phytohaemagglutinin-induced aggregation of leukocytes in platelet-rich plasma, whereas formyl-Met-Leu-Phe-induced aggregation was not affected by antithrombin. Data show that in the presence of plasma and platelets, aggregation of normal white blood cells after stimulation with lectin but not with chemotaxin is inhibited by antithrombin, suggesting specific interactions of antithrombin with lectin-activated processes of neutrophil aggregation that occur in the presence of platelets and/or plasma.
Antithrombin III↗
Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction.
Estimation of cardiac morbidity in patients after major surgery is a difficult problem. In addition, infectious complications seriously decrease potential beneficial outcome after cardiovascular surgery. The present study assessed the use of a newer marker of the inflammatory response, procalcitonin, in the field of myocardial infarction, in conjunction with measurements of interleukin-6. Forty-four consecutive cases with acute myocardial infarction were included in the study 4+/-1.3 h after the onset of symptoms. Plasma levels of procalcitonin and interleukin-6 were obtained at admission, and after 3, 6, 12, 18, 24 and 48 h, using commercially available test kits. The range of levels of interleukin-6 and procalcitonin was about normal at admission. Interleukin-6 levels increased significantly following myocardial infarction, whereas procalcitonin were essentially unchanged, i.e. remained close to the normal level threshold of 0.5 ng/ml; only minor variability occurred with a mean peak level of procalcitonin of 1+/-0.4 ng/ml. Data demonstrate that, in contrast to the acute phase reactant interleukin-6, plasma levels procalcitonin are not significantly elevated during uncomplicated acute myocardial infarction. This observation may support the role of procalcitonin measurements in the differential diagnosis of infectious and cardiovascular complications after major surgery.
Acute-Phase Reaction↗
The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel.
Resting platelets inhibit oxygen radical release from neutrophils. Antiplatelet therapy may support this function by preventing platelet activation. Whether antiplatelet agents affect the antioxidative action of resting platelets in the absence of platelet activation is unknown. The effect of acetylsalicylic acid or clopidogrel administration on the antioxidative action of resting platelets was therefore studied in ten healthy volunteers. Preparations of resting platelets were obtained from 5 subjects each - before, during and after an eight-day course of daily treatment with 100 mg of acetylsalicylic acid or 75 mg of the thienopyridine clopidogrel. Human peripheral blood neutrophils were pretreated with the platelets at a ratio of (1/5)0 for 45 min; then formyl-Met-Leu-Phe-triggered oxygen radical release was measured fluorometrically. The inhibitory effect of platelets on oxygen radical release from neutrophils which was seen before treatment was abolished by antiplatelet therapy with either of the drugs, and inhibition was restored gradually after discontinuing acetlsalicylic acid/ clopidogrel intake. Results suggest that the protective role of resting platelets in controlling oxygen radical release from neutrophils in the absence of platelet activation may be impaired by antiplatelet therapy.
Adult↗
Inhibition of human peripheral blood neutrophil respiratory burst by alcohol-based venipuncture site disinfection.
Ethanol inhibits the respiratory burst of neutrophils. Therefore, the effects of alcohol-based skin disinfection on oxygen metabolism in neutrophils were tested using 70% ethanol or an ethanol-isopropanol-n-propanol mixture. Neutrophil respiratory burst activity as assessed fluorometrically by oxidation of 2', 7'-dichlorofluorescein diacetate increased at 10 min after disinfection with 70% ethanol compared to the activity at 30 s. The increase was significant for triggering oxidative burst with formyl-peptide but not with phorbol myristate acetate.
1-Propanol↗
Neutrophil infiltration into human gliomas.
Human gliomas were analysed for the infiltration of neutrophils using immunohistochemistry by staining sections for CD15-positive and myeloperoxidase-positive cells. Over 70% of all glioma samples analysed (n = 105) had significant neutrophil infiltration, but there was a marked and significant correlation between tumour grade and the extent of the neutrophil infiltration. In the low grade tumours only 40-50% had significant infiltration, while in glioblastoma multiforme over 85% of the samples analysed had significant infiltration. Numbers of neutrophils infiltrating glioblastoma multiforme tumours were also greater than in the other tumour groups. Circulating white blood cell counts were elevated above the normal range in all glioma patients, but this elevation was entirely due to increased numbers of circulating neutrophils. Again, the highest numbers of circulating neutrophils were seen in the glioblastoma multiforme patients. These experiments indicate that glioma-derived factors may directly or indirectly affect the number of circulating neutrophils and influence their infiltration into the tumours.
Bone Marrow↗
Commentary: Free radicals in gliomas: friend or foes?
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Free Radicals↗
CD44 isoforms, including the CD44 V3 variant, are expressed on endothelium, suggesting a role for CD44 in the immobilization of growth factors and the regulation of the local immune response.
Endothelium plays a central role in the regulation of site and inflammation specific leukocyte migration. Some of the mediators involved in leukocyte migration, such as chemokines, can bind to heparan sulfate on the endothelium resulting in immobilization near their sites of production. Because CD44 variants expressing V3 have been shown to carry heparan sulfate side chains and to interact through these side chains with heparan sulfate binding growth factors, we investigated the expression of CD44 variants on endothelium. We found a strong expression of V5, V7-8 and V10 CD44 variants and a weaker expression of V3 and V6 CD44 variants on endothelium by using immuno-histochemistry and by FACS analysis. Expression of CD44 V3 variants was confirmed at both the protein and mRNA levels by Western blotting and by reverse transcriptase-PCR respectively. Expression of CD44 variants was unaffected by IL-1beta, IL-8, TNFalpha, IFNgamma or IL-4 treatment, indicating either constitutive expression of these variants or involvement of other cytokines in their regulation.
Antibodies, Monoclonal↗
Amyloid neuropathy simulating lower motor neuron disease.
We report a 57-year-old man with progressive symmetric weakness and fasciculation affecting the legs. Electromyography revealed fibrillations and neurogenic motor unit potentials in the leg muscles. Biopsy of a motor branch of the obturator nerve revealed axonal degeneration, loss of myelinated nerve fibers, and amyloidosis with deposits of lambda light chains. At 6-month follow-up, the patient manifested sensory and autonomic symptoms, and lambda light chains were first detected in the serum. In this case, diagnosis of amyloidosis remained elusive until motor nerve biopsy.
Amyloid Neuropathies↗
In vitro effects of GM-CSF on mature peripheral blood neutrophils.
GM-CSF can play a crucial role in regulating the neutrophil-mediated inflammatory response. This growth factor is a proliferative stimulus for bone marrow neutrophil stem cell precursors and has at least 3 important roles in regulating neutrophil-mediated immunity: a) a direct effect on the proliferation and development of neutrophil progenitors; b) synergistic activity with other haemopoietic growth factors; c) stimulation of the functional activity of mature neutrophils. The production of GM-CSF may be triggered directly by exogenous factors such as antigens and endotoxins, or indirectly through the release of cytokines by a variety of cells including lymphocytes, activated macrophages and endothelial cells exposed to products of mononuclear phagocytes. Such production of GM-CSF may serve to quickly release mature neutrophils from the bone marrow in response to infections. Moreover, enhancement of the function of mature neutrophils may also augment their ability to migrate to infective sites and then phagocytose and kill pathogens. Increased expression of CD11b/CD18 may play a fundamental part in this mechanism because this receptor is essential for the adhesion of neutrophils to the endothelium. Both phagocytosis and oxidative burst activity increase as a result of the action of GM-CSF and the increased expression of complement- and Fc-receptors can augment opsono-phagocytosis. A further level of neutrophil up-regulation occurs by increasing the functional life span of neutrophils by GM-CSF. Thus, by delaying neutrophil apoptosis, GM-CSF greatly extends the time over which neutrophils may function at inflammatory sites. GM-CSF can thus exert a variety of important regulatory controls of neutrophil function during bacterial infections. Both the number and the functional status of neutrophils is highly regulated by GM-CSF. It is also possible that GM-CSF produced within localised sites of acute inflammation or infection may attract, trap and then activate neutrophils within this site.
Annexin A5↗
Host tissue damage by phagocytes.
Evidence continues to accumulate on the importance of neutrophils (PMNs) and phagocytes in the causation of tissue and endothelial injury that frequently accompanies the inflammatory response. Increased production of superoxide anions in combination with decreased endothelial antioxidant activity may contribute to the development of vascular disease including atherosclerosis, vasospasm, diabetic vascular complications, tissue damage in ischemia-reperfusion, and hypotension. Free radicals generated in the vascular wall may act directly on smooth muscle or interact with each other thus producing biologically active endogenous mediators. Derangement of macrophage function may occur in conditions characterized by protein malnutrition, thus leading to failure to develop a specific immunoresponse and to an increase in the production of oxygen intermediate radicals, which may cause tissue damage. A local inflammatory response followed by endothelial cell activation could also facilitate migration of immunocompetent cells into the parenchyma of grafted organs and stimulate dendritic cells in the graft. There is now convincing evidence that excessive and prolonged production of NO contributes to tissue damage in septicemia, ischemia/reperfusion injury, and other inflammatory conditions. There is also increasing evidence that the complement system plays an important role in tissue damage in association with phagocytes, e.g., in ischemia/reperfusion injury, carcinogenesis, and aging. It can therefore be surmised that phagocytic cells may act both as "friends" and as "foes" and that they are important mediators of tissue damage in a variety of conditions.
Animals↗
Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation.
The aim of this study was to assess the expression of CD11b/CD18 integrin adhesion molecules on the phagocytes of patients with ischaemic diseases, and to evaluate the concentration of soluble adhesion molecules that are released from endothelium (sICAM-1) and from phagocytes (sL-selectin). A total of 370 patients were enrolled: 120 with coronary artery disease (CAD); 50 with peripheral artery occlusive disease (PAOD); and 200 control subjects with no clinical manifestations of ischaemic disease. CD11b/CD18 integrin was detected by flow cytometry, whereas sL-selectin and sICAM-1 concentrations were detected using a sandwich-type immunoassay. CD11b/CD18 integrin expression was found to be higher in the patients with ischaemic disease than in the control subjects (P < 0.001). The PAOD patients had higher values of CD11b/CD18 integrin than the CAD ones (P < 0.01). The concentration of soluble adhesion molecules did not show any significant differences within the three groups (P = NS). The high expression of CD11b/CD18 integrin in ischaemic disease patients may depend on the increased, but probably stable, cytokine network that has been demonstrated to occur in chronic ischaemic diseases: the difference observed between PAOD and CAD patients could be the consequence of higher inflammatory activation probably resulting from the greater extent of the atherosclerotic process in PAOD, or of the more localized ischaemic area in CAD patients. CD11b/CD18 can therefore be considered a marker of chronic phagocyte activation during ischaemic disease. On the other hand, sICAM and sL-selectin concentrations were found to be within the normal range; they have recently been considered as a marker for acute ischaemic events and acute inflammatory process activation. Our results confirm that in uncomplicated atherosclerosis no acute inflammatory process activation should occur.
Blood Coagulation↗
Over expression of alpha M beta 2 integrin on peripheral blood human neutrophils stimulated with GM-CSF.
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Flow Cytometry↗
Expression of neutrophil and monocyte CD11B/CD18 adhesion molecules at different sites of the coronary tree in unstable angina pectoris.
To assess the site of leukocyte activation in unstable angina, the expression of neutrophil and monocyte CD11B/CD18 adhesion molecules in 26 patients was measured from blood samples taken from the coronary ostium, the coronary sinus, and the coronary artery just distal to the culprit lesion (postobstructive chamber). CD11B/CD18 adhesion molecules detected by direct immunofluorescence evaluated by flow cytometry were significantly higher in the coronary sinus blood than in both the coronary ostium and the postobstructive chamber blood, suggesting that leukocyte activation takes place at the microcirculatory interface with the injured myocardium, probably as the result of short but repeated episodes of myocardial ischemia.
Adult↗
Iloprost effects on phagocytes in patients suffering from ischaemic diseases: in vivo evidence for down-regulation of alpha M beta 2 integrin.
This study has been designed to demonstrate the in vivo effects of iloprost therapy on expression of adhesion molecules on phagocytes. Sixty patients suffering from peripheral arterial occlusive disease (PAOD) and/or from skin ulcers due to secondary progressive systemic sclerosis (PSS) were enrolled in a double-blind controlled parallel study. Thirty patients (group I) underwent iloprost infusion and 30 patients (group II) were treated with aspirin. Clinical assessment and measurement of phagocyte activation in vivo, using quantitative flow cytometry, were performed on entry and after 6 h on the first day of therapy. After 3 months of therapy, complete healing of all cutaneous lesions was observed in 84% of the patients treated with iloprost compared with the control patients (P < 0.001). Neutrophils and monocytes of PAOD and PSS patients showed a significant decrease in the expression of the alpha M beta 2 integrin adhesion receptor after 6 h of iloprost infusion. Neutrophils and monocytes released a lower amount of anion superoxide (O2-) after 6 h of iloprost treatment. These data confirm other clinical observations but demonstrate that in vivo this drug modifies the expression of the alpha M beta 2 integrin of phagocytes that has a key role in leukocyte-endothelium interactions in cases of inflammation and thrombosis.
Adult↗
Granulocyte dysplasia and dysfunction, and CD11/CD18 defects in myelodysplastic syndromes.
In myelodysplastic syndromes (MDS), dysplastic changes in neutrophils are a common feature reflecting the total degree of bone marrow dysplasia. Furthermore, granulocyte function is abnormal, so that a high risk of life-threatening infections has been documented. In this review we shall focus on the defects of both granulocytes and their CD11b/CD18 glycoprotein complex, which regulate granulocyte adherence, locomotion, diapedesis and migration into inflammatory sites, in patients suffering from primary MDS. The defective surface membrane glycoprotein expression of myelodysplastic phagocytes is not only a useful diagnostic tool, but also a powerful prognostic one, since MDS patients with such defects present both an increased susceptibility to infections and a decreased survival. Moreover, the administration of colony-stimulating factors is known to be able to elicit long-lasting improvement in neutrophil count, CD11b/CD18 expression and function, marrow myeloid maturation, and possibly to decrease bacterial infections in MDS patients.
CD11 Antigens↗
[Job syndrome (hyper-IgE) and hypo-IgA. A rare association of immunodeficiencies].
Job' syndrome and IgA immunodeficiency are a rare dysfunction of the immune system. In this work, we reported a case of a young woman who had recurrent episodes of bacterial infections in the urinary tract and genital, generalized erythematous eczematous patches and stomatitis of oral mucosa and fever. During the hospitalization, laboratory data showed high immunoglobulin IgE and low IgA levels. The T-lymphocyte presented a reduction of CD8+ cells. Tests of granulocyte function have showed a global deficit in the in vitro and in vivo chemotaxis. The correlation between these two clinic conditions is not completely clarified but it is possible to hypothesize that CD8+ lymphocytes produce an inhibition factor of chemotaxis. Job' syndrome is characterized by a selective reduction of CD8+ cells subpopulation which have an immunoregulatory function on the production of IgE by plasmacells. In the ipoIgA, an intrinsic inability of B-IgA cells to proliferate and to differentiate produce a defect in the IgA production. In these two clinic disorders there is an effective dysfunction of immune system. It is possible to hypothesize that an effective defect of CD8+ cells and an immaturity of B-cells may coexist in our patient. That justifies an abnormal production of Ig and a defect in granulocyte chemotaxis.
Adult↗
Changes in opioid receptor density on murine splenocytes induced by in vivo treatment with morphine and methadone.
In a 24-hr time course study we reported previously that a single systemic injection of morphine profoundly affected various immune parameters in mice. In the present study we examined whether these effects are mediated by changes in opioid receptor density on murine splenocytes after acute in vivo morphine (20 mg/kg s.c.) and methadone (12.5 mg/kg s.c.) at equianalgesic doses. To define the splenocyte subpopulations we used flow cytofluorimetric analysis with specific fluorescent monoclonal antibodies and calculated the binding of the fluoresceinyl opiate antagonist naloxone on opiate receptors. Both morphine and methadone reduced the density of opiate receptors on B- and T-lymphocytes. Specifically, 20 min, 1 and 3 days after the injection there was a marked reduction (about 55%) in naloxone binding sites; these returned to base line after 5 days for T-lymphocytes and after 7 days for B-lymphocytes. Despite the low proportion of macrophages among total splenocytes (about 10%), our results also indicate a tendency to a reduction in opiate receptor density also in the macrophage population. These findings indicate that a single exposure to morphine and methadone results in a strong, lasting down-regulation of opiate binding sites in murine splenocytes, probably accounting for the immunomodulation induced by opiates.
Analgesics, Opioid↗