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S Traniello

Publications and source records attributed to S Traniello.

At least 55 records · Page 3Linked to original sources
PubMed1993

Structure-activity relationships of cyclic and linear peptide T analogues.

Using the potent cyclic peptide T analog [formula: see text] as parent compound, a series of analogues were synthesized and their potencies in a monocyte chemotaxis assay were compared with those of correspondingly modified linear peptides. Structure-activity relationships observed with cyclic compounds did not always parallel those determined with linear analogues. [formula: see text] showed the highest affinity to CD4 receptor of monocytes of any peptide thus far studied. It also proved to be highly resistant to degradation by plasma or brain enzymes.

Amino Acid Sequence↗
PubMed1992

Modulation of neutrophil functions by activated platelet release factors.

Platelets activated with physiological agonists, such as thrombin, ADP, or collagen, released products able to modulate neutrophil functions. In particular, platelet supernatant contained an inhibitor of superoxide anion generation induced by phorbol ester and a chemotactic factor for human neutrophils. The proteolytic digestion of platelet supernatant completely abrogated chemotactic activity without interfering with the inhibitory effect, indicating the presence of different molecules involved in the modulation of different neutrophil functions. This was further confirmed by the pretreatment of platelets with aromatic benzamidine which abolished chemotactic activity, but did not affect superoxide inhibition of neutrophils. This report provides evidence for interaction of platelets and inflammatory cells, suggesting that platelets are able to induce accumulation of neutrophils and control their respiratory burst, which also has a critical role in tissue damaging in inflammation.

Benzamidines↗
PubMed1992

New chemotactic peptide analogs with high biological activity for human neutrophils.

As a part of a research programme aimed at studying structure activity relationships in the field of chemotactic peptides, modified analogs of the chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were examined for their capacity to activate several functions of human neutrophils. 4-Aminotetrahydrothiopyran-4carboxylic acid (Thp) and 2-aminoindane-2-carboxylic acid (Ain) were chosen as achiral, conformationally restricted amino acids suitable for mimicking the external Met and Phe residues of FMLP-OMe. The replacement of both produces a high locomotion activity, greater than the parent peptide; in contrast, the two Thp-containing analogs induce neither superoxide production nor lysozyme release. From these results we can hypothesize two different signal transduction systems: one which provides for movement, the other for superoxide generation and granule enzyme release.

Amino Acid Sequence↗
PubMed1991

CD16 and CR3 receptors distinguish between the two mechanisms of tumour cytotoxicity in neutrophils.

Previous studies have suggested that phorbol ester-activated neutrophils kill both antibody non-coated and antibody-coated K562 target cells. In this report the contribution of the receptors Fc gamma III (CD16) and CR3 (CD11b/CD18) in the lytic process was investigated. In neutrophils CD16 and CR3 are up-regulated by the phorbol ester up to 4 and 10 times, respectively. As expected, lysis of non-immunized K562 targets is not affected by the treatment of neutrophils with anti CD16, AB8.28, whereas lysis of immunized targets is decreased by 50%. In addition, the interaction of CD16 and AB8.28 induces calcium mobilization and increases granule secretion. Surprisingly, the simultaneous binding of AB8.28 and anti-CR3 OKM1 to neutrophils completely abolishes the lysis of antibody-coated targets. Unlike CD16, CR3 does not possess a functional role and binding of OKM1 to CR3 does not affect cytotoxicity of immunized K562 targets, but it blocks lysis of non-coated target almost completely, indicating a function as adhesion protein for CR3. These studies demonstrate a distinct role of CD16 and CR3 in mediating antibody-dependent and antibody-independent cellular cytotoxicity, respectively.

Antibodies, Monoclonal↗
PubMed1991

Evaluation of CR1 expression in neutrophils from chronic myeloid leukaemia: relationship between prognosis and cellular activity.

The expression of the complement receptor CR1 has been evaluated using an immunoalkaline phosphatase staining method on peripheral blood neutrophils and granulocyte precursors from 22 patients with chronic myeloid leukaemia (CML) and 15 healthy subjects. The immunocytochemical labelling pattern of CR1 was evaluated semiquantitatively on cell smears using three different anti-CR1 monoclonal antibodies. The scoring method showed that seven patients with CML had a marked reduction in CR1 expression which did not change with in vitro stimulation of neutrophils with phorbol-myristate-acetate (PMA) whereas control cells responded to PMA, increasing the receptor level two-fold. In addition, functional analysis of neutrophils with low CR1 expression from CML patients showed a very low cytolytic activity against K562 tumour target, suggesting a relationship between the cellular content of CR1 and neutrophil tumouricidal activity. The involvement of CR1 in neutrophil-mediated lysis is consistent with complete lack of tumour toxicity following receptor neutralization by anti-CR1 monoclonal antibodies. Interferon therapy improved CR1 expression and the cytolytic response of neutrophils in three out of five CML patients with a moderately low CR1 score. CML patients non-responding to interferon therapy and those with a very low CR1 score, independent of the clinical stage, progressed more rapidly into the advanced clinical stage and blastic crisis.

Complement C3b↗
PubMed1990

Chemotactic response of human monocytes to pentapeptide analog derived from immunodeficiency virus protein gp 120.

The octapeptide sequence of peptide T is contained within the envelope of HIV and seems to mediate the viral binding to CD4 expressing cells, including monocytes. The biological activity of the alpha-aminobutyric acid pentapeptide derived from the C-terminal sequence of peptide T, in which the polar side chain of threonine in position 4 is substituted by a hydrophilic group, is measured by the monocyte chemotaxis assay. The chemotactic activity of human monocytes is assessed by determining the concentration at which the pentapeptide analog is maximally active and the effectiveness at that concentration, in comparison with peptide T and two shorter homologs, the pentapeptide and tetrapeptide. These experiments suggest that the synthetic analog is a potent chemotactic factor active at picomolar concentrations and that it competes with peptide T for the monocyte binding site.

Chemotaxis, Leukocyte↗
PubMed1990

Dual mechanism in induction of human neutrophil cytotoxicity: activation of protein kinase C and elevation in intracellular calcium.

Human neutrophils can damage the non-immunized K562 cell line when stimulated by phorbol myristate acetate (PMA). The combination of the activation of protein kinase C by phorbol and the increase of free intracellular calcium by ionophore potentiates the lytic reaction. The OKT9-immunized target cells are not able to induce by themselves the lytic response in neutrophils, but by combining the two signals, the antigenic stimulus and PMA, a high level of cytolytic response is attained. The addition of EGTA does not affect neutrophil cytotoxicity against antibody-coated targets, while it markedly reduced the lytic reaction against non-immunized targets; in contrast, the addition of EGTA together with the ionophore ionomycin completely suppresses the lysis of immunized and non-immunized targets. The treatment of neutrophils with the protein kinase C inhibitor H-7 causes a dose-related inhibition of the lytic functions that is greater on unsensitized K562. Thus the interaction of Fc receptors with immunized targets is required for reaching the maximal cytolysis. The enhanced lytic activity that occurs in the presence of immunized targets is mediated by calcium flux, as detected by using the monoclonal antibody AB8.28 which binds to FcIII receptors (FcRIII), thus supporting that both signals are involved.

Antibodies, Monoclonal↗
PubMed1990

Synthesis, metabolic stability and chemotactic activity of peptide T and its analogues.

Acquired immunodeficiency syndrome (AIDS) is initiated by the attachment of the human immunodeficiency virus (HIV) to a surface glycoprotein CD4 present on T4 helper/inducer lymphocytes, monocytes/macrophages and other cells. A simple octapeptide (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, peptide T) seems to inhibit HIV infectivity and to activate human monocyte chemotaxis. In order to study in vitro metabolic stability and structure-activity relationships, peptide T and a number of analogues were prepared and tested on human monocytes by chemotactic assay. Peptide T and the shorter fragments T(3-8)-OH and T(4-8)-OH displayed potent bioactivity (maximal chemotactic activity in the range 10(-11)-10(-10) M). The C-terminal heptapeptide showed a reduction of potency, while further truncations at N-terminus of T(4-8)-OH abolished the biological action. In the octapeptide series, whereas the alpha-amino butyric acid (Abu) substitution for Thr4 was well tolerated, the same "slight" structural change at Thr5 or Thr8 was very detrimental. Finally, [D-Asn6]T(1-8)-OH analogue has low chemotactic activity. All these results indicate that i) the C-terminal pentapeptide is the minimum sequence required for bioactivity, ii) residues 5 to 8 appear to play a crucial biological role, iii) peptide T chemotaxis is mediated, at least in part, through the polar properties of Thr side chains at the critical positions 5 and 8, while the Thr4 does not interfere with biological characteristics of peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Neutrophil defect associated with hairy cell leukemia.

We have investigated the motility, superoxide anion production and tumor cell lysis of neutrophils from five patients affected by hairy cell leukemia. Random locomotion and chemotaxis towards denaturated casein and activated serum was normal as well as the superoxide production by opsonized zymosan. In contrast, chemotaxis and superoxide generation induced by FMLP and TPA were markedly reduced. The low responsiveness of neutrophils to TPA was also observed by evaluating cell lysis, against either non-immunized K562 target cells or antibody-coated tumor targets. In hairy cell leukemia neutrophils showed a selective reduced response to TPA and FMLP that, directly or indirectly, activate PKC, suggesting an impairment in the system of signal transduction.

Cell Movement↗
PubMed1989

Lymphocytes treated with natural alfa-interferon produce a chemotactic factor for human neutrophils.

Lymphocytes stimulated with alfa-interferon released a chemotactic factor for neutrophils. The process was not inhibited by cycloheximide, whereas mepacrine completely inhibited release of the chemotactic activity. The chemotactic factor was resistant to storage, heat treatment and proteolysis. Recombinant alfa-interferon did not stimulate lymphocytes to release a neutrophil chemotactic factor.

Cells, Cultured↗
PubMed1989

Triggering of neutrophil cytotoxicity against an antibody-coated tumour target by TPA.

The human erythroid myeloid leukaemia cell line K562 was used as target for human neutrophil cytotoxicity. Neutrophils demonstrated cytotoxicity against K562 only in the presence of a second stimulus, tetradecanoyl phorbol acetate (TPA), a result consistent with previous observations. We now demonstrate that antibody-coated K562 (using OKT9 and 345 monoclonal antibodies) are similarly only sensitive to neutrophils when TPA is added. The presence of both antibody and TPA in the cytotoxic assay resulted in significantly higher levels of cytotoxicity than in the absence of antibody; the result being consistent with a synergistic action between protein kinase C activation and Fc receptor perturbation in the neutrophil. The cytotoxicity against non-coated and antibody-coated targets was markedly inhibited, particularly against the former, by the protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine (H-7). There were marked differences in the extracellular calcium dependency of the two types of cytotoxicity reactions. TPA-activated respiratory burst was unaffected by the presence of non-coated and OKT9-coated targets, whereas TPA-induced lysosomal enzyme release was significantly increased by non-coated targets and a further increase occurred in the presence of OKT9-coated K562.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Structure-activity relationships of peptide T-related pentapeptides.

Fifteen pentapeptide analogs of C-terminal fragment of peptide T, H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, were prepared and tested for human monocyte chemotaxis. Structure-activity studies suggest that the potent chemotactic activity of H-Thr-Thr-Asn-Tyr-Thr-OH is mediated through the polar properties of the C-terminal carboxyl group and Thr side chains at the critical positions 5 and 8, while the hydroxyl group of N-terminal Thr and its free amino function are not essential requirements for CD4 receptor interactions.

CD4 Antigens↗
PubMed1988

Monoclonal antibodies: modulation of cellular activities and identification of heterogeneity of functional response in human neutrophils.

We have studied the effect of the two antibodies, MF 25.1 and GF 26.7.3, on leucocyte function: these antibodies did not mimic the effect of cellular stimuli, but the pre-treatment of neutrophils with MF 25.1 and GF 26.7.3 modulated several cell activities. Both antibodies significantly reduced superoxide anion production in response to various stimuli. Despite similar cellular response MF 25.1 and GF 26.7.3 bound to different antigenic determinants, as shown both by immunoblotting studies and by treating neutrophils first with GF 26.7.3 and subsequently with MF 25.1, and vice-versa; the inhibition of superoxide production corresponded, in fact, to the total of that seen for each antibody. Moreover, in the absence of attractant, measures of locomotion of neutrophils treated with monoclonal antibody showed that 43% of the subjects responded to antibody binding by twofold activation of spontaneous movement. Chemotaxis and lysosomal enzyme release were not affected by antibody treatment.

Antibodies, Monoclonal↗
PubMed1987

Protein kinase C mediates human neutrophil cytotoxicity.

Human neutrophils stimulated with phorbol myristate acetate were able to damage human erythroleukemic K562 cells, in the absence of specific antibody, as assessed by a two hour 51Cr release assay. Neutrophils treated with formyl-peptide fMet-Leu-Phe did not display tumoricidal response, but the addition of diacylglycerol kinase inhibitor R59022 together with formyl-peptide induced the cytotoxic capacity against tumor target cells. Phorbol ester is a potent activator of certain functions of neutrophils because of its ability to directly and irreversibly stimulate protein kinase C; formyl-peptide, on the contrary, activates protein kinase C by inducing a rapid and transient production of diacylglycerol, that is quickly metabolized. The addition of an inhibitor of diacylglycerol kinase, R59022, however potentiated the action of formyl-peptide. These results indicate that protein kinase C is involved in the tumoricidal activity of neutrophils against K562 cells, and that maximal activation of the enzyme is required to achieve the cytotoxic response.

Cytotoxicity, Immunologic↗