[Derivatives of pyrazole with antiaggregant activity].
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Humans↗
Biomedical subjects
S Traniello
Publications and source records attributed to S Traniello.
Conformational studies of synthetic tripeptide chemoattractants.
The conformational behavior of the chemotactic peptide analogs formylmethionylleucylphenylalanine methyl ester (CHO-Met-Leu-Phe-OMe) and formylmethionylleucylcyclohexylalanine methyl ester (CHO-Met-Leu-Cha-OMe) has been studied in solvents of different polarity by circular dichroism and infrared absorption. Both analogs and very probably the chemotactic peptide formylmethionylleucylphenylalanine (CHO-Met-Leu-Phe-OH) preferably adopt in solution a folded "active" conformation which allows a strong interaction with the receptor on the human polymorphonuclear leukocyte surface.
Chemotaxis, Leukocyte↗
Does a relationship exist between neutrophil myeloperoxidase deficiency and the occurrence of neoplasms?
36 unrelated individuals with neutrophil MPO deficiency, (10 totally MPO deficient) were found on screening a population of 148,000 subjects. A further 2 subjects with total and 22 with partial MPO deficiency were identified through family studies. The assessment of neutrophil function, i.e., peroxidase activity, superoxide anion generation, microbicidal activity towards fungi and bacteria, and locomotor behaviour, was carried out in 10 subjects with total and 4 with partial MPO deficiency. We found that the enzyme defect is associated with a marked impairment in the killing of both S. aureus and C. albicans, without affecting microbicidal activity against S. faecalis. There appears to be a high incidence of malignancy in patients with complete MPO deficiency, suggesting a relationship between a defective MPO system and neutrophil-mediated tumor cell cytotoxicity.
Adolescent↗
Formyl peptide chemoattractants. Synthesis and chemotactic activity.
The tetrapeptides CHO-Met-Leu-Phe-CO-NH-(CH2)n-COOMe (n = 1-5) have been synthesized. These peptides containing an omega-amino acid residue in position 4 exhibit a very high chemotactic activity. Like the chemotactic peptide CHO-Met-Leu-Phe-OMe, these tetrapeptides in solution undoubtedly adopt an "active" conformation which allows a strong interaction with the receptor on the human polymorphonuclear leukocyte surface.
Cell Movement↗
Myelin basic protein inhibits formyl-peptide induced chemotaxis in human neutrophils.
Myelin basic protein, one of the major membrane protein component of the central nervous system, was used to probe the molecular mechanism of cellular activation. Pre-treatment of human neutrophils with myelin basic protein selectively inhibits the formyl-peptide-induced chemotaxis, without affecting chemotaxis evoked by casein and activated serum. Furthermore, both the degranulation and superoxide anion production stimulated by the chemotactic peptide are not modified by the prior treatment of the neutrophils with myelin basic protein.
Calcium↗
Deficiency of neutrophil membrane antigen detected by monoclonal antibody in rheumatoid arthritis.
Monoclonal antibodies (mAbs) against cell surface antigens and receptors are instrumental in defining specific membrane markers. mAbs GF 26.7.3 and MF 25.1 against human neutrophils modulated the activation mechanism of superoxide anion production induced by formyl-peptide and PMA in all subject. However, treatment with mAb MF 25.1 of neutrophils from patients with rheumatoid arthritis did not have any effect. This may suggest that the antigen which MF 25.1 binds is absent in rheumatoid conditions. This confirms our previous data showing that defective expression of membrane components is associated with neutrophil dysfunction.
Antibodies, Monoclonal↗
Response of human neutrophils to formyl-peptide modified at the terminal amino and carboxyl groups.
Two analogs of chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine were examined for their capacity to activate several functions of human neutrophils. The C-terminus methyl ester derivative of the chemotactic peptide was found to possess strong biological activity and was able to induce levels of chemotaxis, enzyme secretion, and superoxide generation comparable to those observed with the same concentrations of N-formyl-L-methionyl-L-leucyl-L-phenylalanine. The analog containing a tert-butyloxycarbonyl group at the N-terminus, as well as the C-terminal methyl ester, was completely devoid of activity towards neutrophils. From these results, it appears that the free carboxyl group is not necessary for biological function. In contrast, the substituent at the N-terminus may play a critical role in the induction of the cellular response.
Chemotaxis, Leukocyte↗
[Morphological, ultrastructural, cytochemical and functional analysis of neutrophils deficient in myeloperoxidase].
Eighteen patients with established hereditary myeloperoxidase deficiency underwent morphological, ultrastructural, cytochemical and functional analysis in order to correlate the lack of peroxidase from phagocytes with other leucocyte activities. Cytochemical and ultrastructural findings only confirmed the peroxidase defect in neutrophil and monocyte population, whereas normal peroxidase activity was detected in eosinophil granulocytes ("Alius-Grignaschi anomaly"). Morphological analysis, as determined by both ligh and electron microscopy, showed in two patients with total MPO-deficiency a large number of neutrophils (50-60%) with nuclear abnormalities very similar to Pelger-Huet's heterozygous form (two lobed neutrophils having a typical pince-nez appearance and a nuclear chromatin coarser than that of normal PMNL). Other 2 cases displayed a 50-60% five-lobed neutrophils, as occur in congenital nuclear hypersegmentation of PMNL. These findings suggest that Alius-Grignaschi anomaly and Pelger-Huet syndrome can be found associated in the same individuals, since both these abnormalities have a genetic origin. Finally, since an impaired bactericidal and fungicidal activity was observed, no patients displayed particular susceptibility to persistent or severe infections, thus confirming the presence of MPO-independent enzymatic systems.
Blood Bactericidal Activity↗
Defective expression of neutrophil membrane proteins in patients with rheumatoid arthritis.
At least 14 iodinated proteins can be distinguished by SDS polyacrylamide gel electrophoresis followed by autoradiography in the membrane of intact human neutrophils. Neutrophils from patients suffering from rheumatoid arthritis show a modified expression of 4 outer membrane proteins. Three polypeptide components of the 30, 50 and 130 K were decreased by 95%, while the 120 K component dramatically increased. The possible relationship between the altered cell sensitivity and the defective expression of membrane proteins is discussed.
Adult↗
[Indomethacin and oxamethacin as modulators of the production of superoxide anion in human leukocytes].
Treatment of human neutrophils with the two chemoattractants formyl-methyonyl-leucyl-phenylalanine and opsonized zymosan or with phorbol myristate acetate induce the production of superoxide anion (O-.2), which plays a role in the inflammatory reaction and microbicidal activity. The time-course of O-.2 release and the extent to which the anion is produced are related to the nature of the stimulating agents. Anti-inflammatory non steroid drugs, such as indomethacin and oxamethacin, exert a variable depression of the oxidative burst, which does not seem correlated to the inhibition of prostaglandin synthesis, but to the lipophilic character of the drug molecule.
Humans↗
[An analog of formyl-met-leu-phe effects the movement of human leukocytes].
Two tripeptides, related to the chemotactic formyl-peptide, are tested for its ability to affect random and directional locomotion and to induce chemotaxis of polymorphonuclear leukocytes. The results indicate that the methyl ester of formyl-methyonyl-leucyl-phenylalanine possesses a biological activity towards human phagocytes, including a chemotactic potency, comparable to that of unmodified peptide. Therefore, the free carboxyl group does not seem essential to generate active leukoattractant. On the contrary, the replacement of the formyl group by the butyloxycarbonyl results in a drastic loss of biological activity. Our data may indicate that the two formyl-peptides interact with the same binding site on the cell membrane.
Binding Sites↗
Effect of antiinflammatory agents on neutrophil superoxide production in rheumatoid arthritis.
Granulocyte superoxide production by different stimuli was studied in 14 patients suffering from rheumatoid arthritis, and in four cases defective O(2) generation was shown. The effect of two chemically related drugs, such as indomethacin and oxamethacin, was also evaluated, since we have previously investigated the action of antiinflammatory agents on cell locomotion. Indomethacin did not affect O(2) production, whereas oxamethacin reduced significantly superoxide generation in PMNs from all subjects tested. Moreover, the extent of the effect was dependent on the stimulant used, being larger when the activation of O(2) generating system was induced by opsonized zymosan.
Anti-Inflammatory Agents↗
Impaired HLA capping capacity of peripheral blood lymphocytes in Duchenne muscular dystrophy.
The cap capacity in nine Duchenne muscular dystrophy (DMD) patients and in 23 healthy male subjects (14 adults and nine neonates) has been investigated by inducing capping of HLA molecules. The evaluation of capping percentages ranged in healthy controls from 44 to 61 with a mean value of 53.39 +/- 4.89, while DMD patients displayed cap capacity of percentages varying from 15 to 38 with a mean value of 31.5 +/- 7.42. Statistical significance of the differences between the two groups, assessed by the Mann-Whitney U test, was p less than 0.00003. A correlation was found in DMD patients between cap capacity and age (tau = +0.657, p = 0.012). The results confirm previous reports of Ig capping impairment noted in B cells of the whole lymphocyte population, supporting the hypothesis of a systemic cellular defect in DMD patients. The data obtained suggest that HLA capping could overcome some of the technical difficulties of Ig capping and could be used as a diagnostic aid in antenatal detection of DMD.
Adult↗
Effect of anti-inflammatory drugs on leukocyte superoxide production by soluble and particulate stimuli.
When polymorphonuclear leukocytes are treated with soluble and particulate substances the cells produce superoxide anion O2-. which plays a role in the activation of the oxidative metabolism. The time-course of O2-. release and the extent to which the anion is produced are related to the nature of the stimulating agents. Anti-inflammatory non steroid drugs, such as indomethacin and oxamethacin, exert a variable depression of the oxidative burst, which does not seem correlated to the inhibition of prostaglandin synthesis.
Anti-Inflammatory Agents↗
Chemotactic behaviour of peripheral and synovial neutrophils during rifamycin SV therapy in rheumatoid arthritis.
The effect exerted by rifamycin SV, used intra-articularly in the treatment of rheumatoid arthritis, on polymorph function was studied. Random and directional locomotion of synovial fluid neutrophils was compared with that of peripheral blood cells in 10 patients followed up during 5 drug applications. PMNs from the two sources were characterized by different responsiveness to this pharmacological agent: blood cells activated chemotaxis in a dose-response way during rifamycin therapy, whereas synovial polymorphs did not modify their locomotor behaviour. It is proposed that the presence of immune complexes and/or factors produced by cell-cell interactions in the articular space may change the synovial neutrophil response to stimuli.
Adolescent↗
[Regulation of the functions of human leukocytes by oxametacine].
Non steroidal anti-inflammatory drugs, such as oxametacine, are generally used in treatment of rheumatoid disease. In an 'in vitro' experimental model, the drug efficacy was tested on leukocyte functions. Locomotion, both random and directional, phagocytic activity and superoxide production of normal and rheumatoid PMNL were tested in the presence of varying concentrations of oxometacine. Locomotion was evaluated by using modified Boyden chambers; phagocytosis was tested by number of yeast particles injested and by NBT reduction; superoxide production was assayed by reduction of ferricytochrome C. In our conditions the drug exhibited a strong anti-inflammatory effect. In fact, chemotaxis and anion production were specifically depressed in a dose-dependent way.
Arthritis, Rheumatoid↗
Interaction between neutrophils and mediators of inflammation.
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Cell Movement↗
Synthetic prostaglandin1 analogue: in vitro studies on human neutrophils.
Prostaglandin (PG) E1 and chemically related compounds 15 alpha-11-deoxy-8-azaPGE1 and 15 epi-11-deoxy-8-azaPGE1 were examined in vitro for their capacity to modulate some physiological functions of human polymorphonuclear leukocytes (PMN). PGE1 was completely devoid of chemotactic activity and did not affect leukocyte phagocytosis. On the contrary, 15 alpha-11-deoxy-8-azaPGE1 showed a potent leukotactic activity. In addition, this synthetic substance significantly depressed the phagocytic activity and the concomitant NBT reduction by leukocytes. The analogue 15 epi-11-deoxy-8-azaPGE1 did not exert any of these effects. From these results it appeared that the substitution of the carbon-8 by the nitrogen and the lack of hydroxyl group at the position 11 into the PGE1 structure, make the compound active towards human neutrophils.
Alprostadil↗