Giovanni Florio

HIV-1 gp120 induces IL-4 and IL-13 release from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE.

HIV-1 glycoprotein (gp) 120 from different clades is a potent stimulus for IL-4 and IL-13 release from basophils purified from healthy individuals seronegative for Abs to HIV-1 and HIV-2. IL-4 mRNA, constitutively present in basophils, was increased after stimulation by gp120 and was inhibited cyclosporin A and tacrolimus. IL-4 and IL-13 secretion from basophils activated by gp120 was not correlated. There was a correlation between the maximum gp120- and anti-IgE-induced IL-4 release from basophils. The average t1/2 gp120-induced IL-4 release was lower than for IL-13 release. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released IL-4 in response to gp120 or to anti-IgE. The response to a mAb cross-linking the α-chain of high-affinity receptor for IgE (FcεRI) was unaffected by this treatment. Three human VH3+ monoclonal IgM inhibited gp120-induced secretion of IL-4 from basophils. In contrast, VH6+ monoclonal IgM did not inhibit the release of IL-4 induced by gp120. Synthetic peptides distant from the NH2 and COOH termini of gp120MN inhibited the activating property of gp120MN. These results indicate that gp120, which acts as a viral superantigen, interacts with the VH3 region of IgE to induce the release of IL-4 and IL-13 from human FcεRI+ cells.

Molecular and Cellular Biology of Mast Cells and Basophils

In all mammalian species investigated so far, mast cells and basophils are the only cells that synthesize histamine and express plasma membrane receptors that bind IgE with high affinity (Fc epsilonRI). Human basophils and mast cells derive from distinct precursors that originate in the bone marrow and fetal liver and probably circulate in peripheral blood. There is extensive evidence that mast cells and basophils and their mediators are primary effectors of allergic inflammation. Immunologically activated human basophils release two cytokines: IL-4 and IL-13. Expression of several cytokines has been documented in a number of experimental models of human and rodent mast cells. However, to date few studies have analyzed the mechanisms of gene expression in human Fc epsilonRI+ cells. Some of these studies imply a role for NFAT and GATA family members in the IgE-mediated activation of cytokine gene transcription in basophils and mast cells. Studies of human basophils and mast cells isolated from different anatomic sites have established the different profiles of eicosanoids released by these cells. Recently, the characterization of arachidonic acid pools and the identification of novel enzymes involved in arachidonate remodeling and mobilization clarified in part how eicosanoid productions is regulated in mast cells and basophils. In addition to histamine, human mast cell secretory granules contain the neutral proteases tryptase, chymase and carboxypeptidase that possess several biochemical properties. In particular, tryptase may play a role as a fibrogenic factor and chymase might convert angiotensin I to angiotensin II. Mast cells are present in human heart and in human coronary arteries raising the possibility that local activation of cardiac mast cells might contribute to certain cardiovascular diseases. Recent evidence also suggests that mast cells and basophils can play a role during viral and bacterial infections. It is now evident that in man these two cells not only participate in inflammation associated with allergic disease, but also in chronic and fibrotic disorders affecting several organs and in host defense against bacterial and viral infections.

Bacterial Immunoglobulin Superantigen Proteins A and L Activate Human Heart Mast Cells by Interacting with Immunoglobulin E

ABSTRACT Human heart mast cells (HHMC) have been identified in heart tissue, perivascularly, and in the intima of coronary arteries. In vitro activation of isolated HHMC induces the release of vasoactive and proinflammatory mediators (histamine, tryptase, and cysteinyl leukotriene C4 [LTC4]). We investigated the effects of several bacterial proteins on HHMC activation in vitro. HHMC released histamine, tryptase, and LTC4 in response toStaphylococcus aureus Cowan 1 and the immunoglobulin (Ig)-binding protein A, but not to S. aureus Wood 46, which does not synthesize protein A. The effect of protein A was inhibited by preincubation with monoclonal IgM VH3+. Some strains of Peptostreptococcus magnus express an Ig light chain-binding surface protein called protein L. Such bacteria and soluble protein L stimulated the release of preformed and newly synthesized mediators from HHMC. Preincubation of HHMC with either protein A or protein L resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus or anti-IgE. Monoclonal IgE (κ chains) blocked protein L-induced release, whereas IgE (λ chains) had no effect. Streptococcal protein G, formyl-containing tripeptide, and pepstatin A did not activate HHMC. Bacterial products protein A and protein L and intact bacteria (S. aureus and P. magnus) activate HHMC by acting as Ig superantigens.

The Campanian Plain and Phlegrean Fields : structural setting from potential field data

Abstract A boundary analysis of the gravity and magnetic fields of the Phlegrean Fields volcanic area and of the surrounding Campanian Plain reveals a complex structural setting. The Campanian Plain results well defined from sharp density boundaries. A set of major E–W lineaments occurs within the Plain. We derive a framework of the structural control to the volcanological evolution of Campanian Plain, which appears strongly influenced by a set of NE–SW lineaments bordering the Acerra depression. The density and magnetization boundaries of the Phlegrean Fields are significantly consistent, both indicating for the collapsed Phlegrean caldera an area considerably less extended than that based on previous geologically-defined models. Many other structures are evidenced in the Phlegrean area, often with agreement between density and magnetization boundaries. Inside the caldera, a strong consistence between the structures we identified and recent seismicity has been noted.

Multiridge analysis of potential fields: Geometric method and reduced Euler deconvolution

A new method based on 3D multiridge analysis of potential fields assumes a 3D subset in the harmonic region and studies the behavior of potential field ridges, which are built by joining extreme points of the analyzed field computed at different altitudes. Three types of ridges are formed by searching for the zeros of the first horizontal and first vertical derivatives of the potential field (types I and II, respectively) and the zeros of the potential field itself (type III). This method uses a redundant set of ridges, called a multiridge set, to determine source type and location. For homogeneous potential fields generated by simple sources, all of the ridges are straight lines converging to the source position. This method analyzes the multiridges by using a geometric criterion to find the source position at the intersection of the multiridge set and by solving the three reduced Euler equations associated with ridge types I, II, and III. The reduced Euler type I and II equations are used to obtain the structural index and the vertical and horizontal source positions; equation type III estimates the horizontal and vertical source positions. Tests on synthetic as well as the Bishop model field yield good results even with noise-corrupted data. Results obtained using magnetic data collected over the wreck of a military ship in the Tyrrhenian Sea successfully determine its vertical and horizontal positions and the structural index.

Human mast cells and basophils in HIV-1 infection.

Mast cells and basophils (FcvarepsilonRI(+) cells) are classically involved in allergic disorders. HIV-1 glycoprotein gp120 acts as a viral superantigen by interacting with the heavy chain, variable 3 (V(H)3) region of IgE to induce cytokine release from FcvarepsilonRI(+) cells. The chemokine receptors CCR3 and CXCR4, co-receptors for HIV-1, are expressed by FcvarepsilonRI(+) cells. Via its interaction with CCR3, HIV-1 transactivation (Tat) protein is a potent chemoattractant for FcvarepsilonRI(+) cells. Incubation of basophils with Tat protein upregulates the surface expression of the CCR3 receptor. There is some evidence that human FcvarepsilonRI(+) cells could be infected in vitro by M-tropic HIV-1 strains.

Gravity modelling of the litho-asthenosphere system in the Central Mediterranean

Abstract The results of the 2.5-D gravity modelling of the litho-asthenosphere system in the Central Mediterranean, along two regional geotransects, are presented and their possible implications for the geodynamical evolution of this area are discussed. Particularly, gravity data on the Tyrrhenian and Provencal-Balearic basins were interpreted introducing significant constraints by means of several main petro-physical parameters tied to the litho-asthenospheric evolution during the extensive tectonics. By this approach, based on the model of McKenzie and Bickle (in: J. Petrol., 29. pp. 625–679. 1988) and White and McKenzie (in: J. Geophys. Res., 94, B6, pp. 7685-7729, 1988), the estimation of the vertical density distribution in the lithosphere-asthenosphere system has been possible. Significant differences in the gravity anomaly field occur when different density models of asthenospheric upwelling are considered. This depends on factors like the thermal regime, the stretching of the lithosphere and its thickness before it. The obtained results contributed to the validation of models interpreting the origin of the Tyrrhenian and Ligurian-Provencal basins as related to a passive extensional process rather than to the presence of an active upwelling asthenosphere beneath the Central Mediterranean basins.

On the application of Euler deconvolution to the analytic signal

Standard Euler deconvolution is applied to potential-field functions that are homogeneous and harmonic. Homogeneity is necessary to satisfy the Euler deconvolution equation itself, whereas harmonicity is required to compute the vertical derivative from data collected on a horizontal plane, according to potential-field theory. The analytic signal modulus of a potential field is a homogeneous function but is not a harmonic function. Hence, the vertical derivative of the analytic signal is incorrect when computed by the usual techniques for harmonic functions and so also is the consequent Euler deconvolution. We show that the resulting errors primarily affect the structural index and that the estimated values are always notably lower than the correct ones. The consequences of this error in the structural index are equally important whether the structural index is given as input (as in standard Euler deconvolution) or represents an unknown to be solved for. The analysis of a case history confirms serious errors in the estimation of structural index if the vertical derivative of the analytic signal is computed as for harmonic functions. We suggest computing the first vertical derivative of the analytic signal modulus, taking into account its nonharmonicity, by using a simple finite-difference algorithm. When the vertical derivative of the analytic signal is computed by finite differences, the depth to source and the structural index consistent with known source parameters are, in fact, obtained.

HIV-1 Envelope gp41 Peptides Promote Migration of Human FcεRI+ Cells and Inhibit IL-13 Synthesis Through Interaction with Formyl Peptide Receptors

We evaluated the effects of synthetic peptides (2017, 2019, 2020, 2021, 2023, 2027, 2029, 2030, 2031, and 2035) encompassing the structure of HIV-1MN envelope gp41 on both chemotaxis of human basophils and the release of preformed mediators (histamine) and of cytokines (IL-13). Peptides 2019 and 2021 were potent basophil chemoattractants, whereas the other peptides examined were ineffective. Preincubation of basophils with FMLP or gp41 2019 resulted in complete desensitization to a subsequent challenge with homologous stimulus. Incubation of basophils with low concentration (5 × 10−7 M) of FMLP, which binds with high affinity to N-formyl peptide receptor (FPR), but not to FPR-like 1, did not affect the chemotactic response to a heterologous stimulus (gp41 2019). In contrast, a high concentration (10−4 M) of FMLP, which binds also to FPR-like 1, significantly reduced the chemotactic response to gp41 2019. The FPR antagonist cyclosporin H inhibited chemotaxis induced by FMLP, but not by gp41 2019. None of these peptides singly induced the release of histamine or cytokines (IL-4 and IL-13) from basophils. However, low concentrations of peptides 2019 and 2021 (10−8–10−6 M) inhibited histamine release from basophils challenged with FMLP but not the secretion caused by anti-IgE and gp120. Preincubation of basophils with peptides 2019 and 2021 inhibited the expression of both IL-13 mRNA, and the FMLP-induced release of IL-13 from basophils. These data highlight the complexity of the interactions between viral and bacterial peptides with FPR subtypes on human basophils.

Immunological modulation of human cardiac mast cells

Human mast cells, by elaborating various cytokines, chemokines and proinflammatory mediators play a complex role in several allergic and inflammatory disorders. Mast cells have been identified in human heart tissue in close proximity to the sarcolemma, in perivascular and adventitial locations and in the shoulder region of coronary atheroma. Human heart mast cells (HHMC) can be isolated from patients undergoing heart transplantation and can be immunologically activated in vitro to induce the release of tryptase, chymase, cysteinyl leukotriene C4 and prostaglandin D2. Several cytokines (e.g., stem cell factor and TNF-α) reside in secretory granules of HHMC. Mast cell density is increased in the hearts of patients with ischemic and idiopathic dilated cardiomyopathy. Cardiac mast cells might contribute to the evolution of atherosclerosis, dilated cardiomyopathy, cardiac and systemic anaphylaxis through the release of cytokines and vasoactive and proinflammatory mediators.