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R Fumarulo

Publications and source records attributed to R Fumarulo.

At least 19 recordsLinked to original sources
PubMed2001

Nicotine effects on polymorphonuclear cell apoptosis and lipopolysaccharide-induced monocyte functions. A possible role in periodontal disease?

Apoptosis provides a mechanism for clearance of unwanted cells in a variety of situations in which programmed or physiological cell death occurs; but the premature death of defensive cells could promote infection, inflammation and concomitant disease. We detected high values of apoptosis in polymorphonuclear cells (PMN) elicited from crevicular sulci of smokers affected by adult periodontitis. To learn more about the effects of nicotine on the periodontal environment, we studied its ability to modulate the apoptosis of two phagocytic lines, PMN and mononuclear cells, which are continuously recruited from gingival vessels to prevent or control plaque extension. Brief exposure of PMN to nicotine concentrations ranging from 0.01 to 0.3% shortened, in a dose-dependent relationship, the lag culture time required to observe at fluorescent microscopy the morphological traces of apoptosis. These observations were confirmed by specific tools of apoptosis: DNA fragmentation on gel electrophoresis and expression of the apoptosis-signaling receptor Fas/Apo-1. The apoptotic effect excited by nicotine on these first line defensive cells may be an important feature of the pathogenesis of periodontal disease. As for mononuclear leukocytes, nicotine was unable to induce apoptotic modifications on cells observed up to 72 h culture time, but the drug inhibited IL-1beta release and procoagulant activity (PCA) expression. The conflicting role played by these lipopolysaccharide (LPS)-induced monocyte functions in the inflammatory process is a further intrigue in the mechanism by which nicotine compromises the oral health.

Apoptosis↗
PubMed1998

Sulfide enhancement of PMN apoptosis.

Hydrogen sulfide is a toxic metabolite released by several bacterial agents under anaerobic conditions. In the present paper, we investigated the effects of sulfide on polymorphonuclear cell (PMN) apoptosis, a mechanism suggested for limiting the toxic potential of neutrophils in inflammatory sites. We showed that 1 mM sulfide (concentration not conditioning PMN viability) is able to enhance the apoptotic fate of human granulocytes by increasing: i) the number of cells containing pyknotic nuclei, ii) the internucleosomal cleavage, and, iii) the intensity of tubulin immunofluorescence staining. The sulfide effect is partially prevented by ionomycin and this finding is consistent with the hypothesis of the inhibiting role played by high levels of cytosolic calcium in PMN apoptosis modulating.

Apoptosis↗
PubMed1997

Sulfide influence on polymorphonuclear functions: a possible role for Ca2+ involvement.

Polymorphonuclear cells (PMN) of gingival sulcus play an important role in host defense against periodontal tissue-invading bacteria, but their phagocytic activity is conditioned by several virulence factors released by oral pathogens. In this report we have studied the influence of sulfide, a toxic bacterial metabolite, on the main PMN functions: chemotaxis, degranulation and oxidative burst. PMN exposed to sodium sulfide (up to 2 mM) used as a source of H2S showed a depression of the calcium-dependent cytoskeleton activities such as chemotaxis and azurophilic granule release induced by FMLP. No effect was observed on the calcium-independent specific granule release obtained by PMA. These data were in agreement with the sulfide inhibition of cytosolic free Ca2+ concentration [Ca2+]i increase normally induced by ionomycin. On the other hand, hydrogen sulfide was able to prime PMN for a stronger oxidative response both to calcium-dependent or calcium-independent stimulation. This finding may account for a more efficient oxidative killing under reoxygenation of the anaerobic infectious areas.

Calcium↗
PubMed1994

Downregulation of human polymorphonuclear cell activities exerted by microorganisms belonging to the alpha-2 subgroup of Proteobacteria (Afipia felis and Rochalimaea henselae).

Intracellular pathogens have evolved effective mechanisms in order to survive in an intracellular environment, thus avoiding destruction by phagocytic cells. In this regard, a correlation between resistance to phagocytic killing and expression of pathogenic potency has been established. In this report, we have studied the interaction between human polymorphonuclear cells (PMN) and two gram-negative microorganisms, Afipia felis and Rochalimaea henselae, which belong to the alpha-2 subgroup of the class Proteobacteria. A. falis has been previously proposed as the causative agent of Cat Scratch Disease (CSD), but several recent lines of evidence attribute a major role to R. henselae. Of note, CSD is a syndrome characterized by a chronic lymphoadenopathy, involving macrophages and endothelial cells with a progression towards a granulomatous process and/or angiogenesis. Since members of the alpha-2 subgroup of Proteobacteria have the property to survive intracellularly, we have evaluated the effects exerted by A. felis and R. henselae on human PMN in terms of chemotaxis locomotion, degranulation and oxidative metabolism. Results will show an impairment of PMN activities as a consequence of the challenge with both microrganisms. In particular, inhibition of PMN oxidative function occurred either as result of a direct exposure to both A. felis and R. henselae or when PMN were primed by bacteria for the N-formyl-methionyl-leucyl-phenylalanine enhancement of the oxidative burst. These findings may account for the ability of A. felis and R. henselae to survive within PMN as expression of a further mechanism of pathogenic potency, influencing also the nature and the evolution of inflammatory response in the lesion sites.

Bartonella henselae↗
PubMed1993

Salivary effects on polymorphonuclear leukocyte functions.

Respiratory burst, enzymatic degranulation and bacterial killing were investigated on peripheral blood polymorphonuclear leukocytes (polymorphonuclear leukocytes) incubated with a pool of salivary fluids elicited from healthy donors. Low saliva concentrations primed polymorphonuclear leukocytes for enhancement of O2 consumption, O2- and beta-glucuronidase release and Staphylococcus aureus killing. Whole saliva, on the contrary, depressed all tested phagocytic activities.

Adult↗
PubMed1991

Inhibitory effect of retinoids on the generation of procoagulant activity by blood mononuclear phagocytes.

Retinoids are known to modulate several functions of mononuclear phagocytes. We have studied the effect of retinyl acetate (RAc) and retinoic acid (RA) on the production of procoagulant activity (PCA) by human peripheral blood mononuclear cells stimulated with endotoxin (1 microgram/ml, 4 or 20 h at 37 degrees C). Both compounds caused a dose-dependent reduction in the expression of cell-associated PCA (from 86 to less than 10% of control in the range of concentration comprised between 0.1 and 100 microM). This effect was also observed when the cells were exposed to retinoids for 10 min and washed before challenge with endotoxin, indicating that it is rapid and irreversible. In contrast, incubation of RAc or RA for 3 h at 37 degrees C with cells that have been already stimulated with endotoxin (20 h at 37 degrees C) remained without influence on cell PCA. The inhibitory action of retinoids was also observed when monocyte-enriched (greater than 85%) preparations or highly purified monocyte-derived macrophages (greater than 99%) were used instead of whole mononuclear cells. BW755C, an inhibitor of cyclo-oxygenase and lipoxygenase, reversed the inhibitory effect of retinoids, whereas acetylsalycilic acid, an inhibitor of cyclo-oxygenase, was inactive, suggesting the involvement of a lipoxygenase product. The inhibition of monocyte/macrophage PCA production and the subsequent reduction of cell potential for fibrin deposition might represent one of the mechanisms whereby retinoids exert their antiinflammatory and immunomodulatory activities.

Blood Coagulation↗
PubMed1991

Retinoids inhibit the respiratory burst and degranulation of stimulated human polymorphonuclear leukocytes.

Retinoids exhibit a wide spectrum of activities, including antiinflammatory properties. We have investigated the effect of retinoic acid (RA) and retinyl acetate (RAc) on the production of reactive oxygen metabolites and the release of lysosomal enzymes by human polymorphonuclear leukocytes (PMN). Incubation of PMN with RAc or RA (1-100 microM) caused a dose-dependent inhibition (upto 90%) in O2- production and chemiluminescence induced by phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylanaline (fMLP), opsonized zymosan or ionophore A23187. Both retinoids (1-100 microM) also inhibited, in a dose-dependent way, degranulation induced by fMLP (upto 85% at the highest concentration of RA). These inhibitory effects appear irreversible, since they persist after the drugs are removed and the cells washed before stimulation. Inhibitors of cyclo-oxygenase activity such as acetylsalicyclic acid and indomethacin did not influence the effects of RAc. In contrast, BW755, an inhibitor of both cyclooxygenase and lipoxygenase, reversed the inhibitory action of RAc, suggesting that the effect of retinoids occurs possibly through the mediation of lipoxygenase products. The modulation of PMN oxidative metabolism and degranulation might help explain the antiinflammatory properties of retinoids.

Calcimycin↗
PubMed1990

Inhibition of neutrophil functions by scrapie prion protein: description of some inhibitory properties.

The effect of scrapie prion protein (PrP) either in the native or in the denatured form was studied on in vitro responses of human neutrophils. Incubation of neutrophils with native PrP caused an inhibition of their aggregation induced by cytochalasin B. Moreover, the denatured form was in itself a strong aggregation inducer. When evaluating the effect on generation of neutrophil superoxide anion (O2) we found that neutrophils released O2 in response to the denatured from only but the native form was ineffective. Similarly, neutrophil discharge of beta-glucuronidase which represents the azurophilic granule marker was stimulated in a dose-dependent form by the denatured PrP 27-30 whereas the native form was almost completely devoid of any activity. These results indicate that several aspects of neutrophil function can be altered by the native form of prion protein PrP 27-30. This might be responsible for the impaired phagocytic cell activity explaining, at least in part, the absence of any inflammatory reaction during scrapie infection.

Cell Aggregation↗
PubMed1989

Different priming on human neutrophil respiratory burst by lipopolysaccharides from phase I and phase II Coxiella burnetii.

Human neutrophils produce small amounts of superoxide anion when stimulated with the chemotactic peptide FMLP; preincubating neutrophils with low concentrations of lipopolysaccharides (LPS) markedly increases this response, an effect referred to as priming. In this work LPS from Coxiella burnetii either phase I (virulent) or phase II (avirulent) were examined for their ability to induce priming. Results clearly show that only LPS from phase II microorganism was able to increase the release from neutrophils upon subsequent stimulation with FMLP. This effect was abolished by preincubation of LPS with polymyxin B. This finding may account for the ability of Coxiella burnetii phase I to escape intracellular phagocyte killing during persistent infections.

Coxiella↗
PubMed1989

Thymomodulin increases the depressed production of superoxide anion by alveolar macrophages in patients with chronic bronchitis.

Thymomodulin is an immunomodulating agent which is derived from calf thymus by partial acid lysis. It promotes T-cell maturation, enhances antibody synthesis and improves the phagocytic response of neutrophils. Clinical trials have revealed the effectiveness of this thymic derivative in the prevention of recurrent respiratory infections (RRI) in children and in adults; 11 patients (8 males and 3 females; age range 18-76 years) with chronic bronchitis dominated by recurrent respiratory infections were studied. They were treated orally for 6 months during the winter season with 120 mg/day of thymomodulin. All the subjects were asked to keep a diary recording the intensity of their symptoms, the number of working days lost (days of illness) and the use of antibiotic and/or mucolytic drugs. At the beginning and at the end of the trial each patient was subjected to a control with a flexible fibreoptic bronchoscope with bronchoalveolar lavage to evaluate the phagocytic response of alveolar macrophages. At the end of therapy a significant improvement of the clinical status, evaluated by the above-mentioned parameters, of the bronchial mucosa aspect and an increase in alveolar macrophage superoxide production was noticed (from 0.1 +/- 0.09 and 0.8 +/- 0.5 nmol to 1.6 +/- 0.8 and 4.1 +/- 2.2 nmol with PMA or zymosan particles respectively; p less than 0.001). During thymomodulin treatment no side-effects were recorded.

Adolescent↗
PubMed1986

Cytochrome b and FAD content in polymorphonuclear leucocytes in a family with X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD), an immunodeficiency syndrome characterized by extreme susceptibility to bacterial infections, is due to a defect of the respiratory burst in human phagocytes. NADPH oxidase, the enzyme that catalyzes the reduction of oxygen and the release of oxidative radicals, was studied in polymorphonuclear leucocytes (PMNs) in a family affected by an x-linked inheritance form at high penetrance of the disease. The contents of cytochrome b, suggested as the terminal component of the oxidase electron transport chain, and FAD, the hypothetical proximal component of the chain, were determined in patients and in carriers. Cytochrome b showed the typical behaviour of x-linked CGD: total absence in patients, intermediate values in carriers. FAD content evaluated on plasma membranes was less decreased than cytochrome b. Carriers also showed a decrease of this flavoprotein. Cytochrome b and FAD contents were compared to NBT test and superoxide production: a clear correlation was observed for the cytochrome b, but FAD plasma membrane evaluation could also be an interesting tool for the metabolic characterization of the disease in patients and in carriers.

Adult↗
PubMed1985

In vitro cisplatin effects on phagocyte functions.

The effects of cis-diamminedichloroplatinum (II) (cisplatin), a drug used in cancer chemotherapy, on the oxidative metabolism, endocytosis, chemotaxis and exocytosis of guinea-pig polymorphonuclear leukocytes were studied. All these functions were negatively influenced, but the same effect (50% inhibition) was observed at different drug concentrations (3 X 10(-5) M for chemotaxis, 10(-4) M for O2 consumption by FMLP and beta-glucuronidase release, 10(-3) M for O2 consumption by PMA and for zymosan engulfment). The effects of the drug can be explained by its ability to bind to membrane proteins, essentially to -SH groups.

Animals↗
PubMed1984

Effect of cisplatin on the oxidative metabolism of polymorphonuclear leukocytes in cancer patients.

Peripheral blood polymorphonuclear leukocytes of patients with ovarian or uterine-cervix carcinoma were studied during cisplatin chemotherapy for phagocytic oxidative metabolism. In particular, superoxide production by these leukocytes after stimulation with opsonized Zymosan particles was determined. The basal value of oxidative metabolism of leukocytes from neoplastic patients was lower than in normals. Superoxide production decreased after each dose administration, but returned to normal at the end of the entire chemotherapeutic treatment. It is suggested that cisplatin treatment, despite a short-lived depression of oxidative metabolism in polymorphonuclear cells, improves this function, most probably by interfering with neoplastic growth.

Cisplatin↗