scholarly journals Superantigenic Activation of Human Cardiac Mast Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1828 ◽  
Author(s):  
Varricchi ◽  
Loffredo ◽  
Borriello ◽  
Pecoraro ◽  
Rivellese ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Heart ◽  
De Novo ◽  
Protein A ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Protein L ◽  
Variable Regions ◽  
Cysteinyl Leukotriene ◽  
High Affinity Receptor

B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.

scholarly journals HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 208
Author(s):  
Giancarlo Marone ◽  
Francesca Wanda Rossi ◽  
Antonio Pecoraro ◽  
Valentina Pucino ◽  
Gjada Criscuolo ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Lung ◽  
De Novo ◽  
Pulmonary Diseases ◽  
Prostaglandin D2 ◽  
Variable Regions ◽  
Cysteinyl Leukotriene ◽  
Chronic Pulmonary Diseases ◽  
High Affinity Receptor ◽  
Hiv Gp120

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.

scholarly journals IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 145
Author(s):  
Leonardo Cristinziano ◽  
Remo Poto ◽  
Gjada Criscuolo ◽  
Anne Lise Ferrara ◽  
Maria Rosaria Galdiero ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Lung ◽  
Protein A ◽  
Protein L ◽  
Variable Regions ◽  
Prolonged Incubation ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Pleiotropic Functions

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are strategically located in different compartments of human lung, where they play a role in several inflammatory disorders and cancer. Immunoglobulin superantigens (e.g., protein A of Staphylococcus aureus and protein L of Peptostreptococcus magnus) bind to the variable regions of either the heavy (VH3) or light chain (κ) of IgE. IL-33 is a cytokine expressed by epithelial cells that exerts pleiotropic functions in the lung. The present study investigated whether immunoglobulin superantigens protein A and protein L and IL-33 caused the release of inflammatory (histamine), angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The results show that protein A and protein L induced the rapid (30 min) release of preformed histamine from HLMCs. By contrast, IL-33 did not induce the release of histamine from lung mast cells. Prolonged incubation (12 h) of HLMCs with superantigens and IL-33 induced the release of VEGF-A and VEGF-C. Preincubation with IL-33 potentiated the superantigenic release of histamine, angiogenic and lymphangiogenic factors from HLMCs. Our results suggest that IL-33 might enhance the inflammatory, angiogenic and lymphangiogenic activities of lung mast cells in pulmonary disorders.

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

2000 ◽  
Vol 68 (10) ◽  
pp. 5517-5524 ◽  
Author(s):  
Arturo Genovese ◽  
Jean-Pierre Bouvet ◽  
Giovanni Florio ◽  
Bärbel Lamparter-Schummert ◽  
Lars Björck ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Heart ◽  
Immunoglobulin E ◽  
Protein A ◽  
Surface Protein ◽  
Heart Tissue ◽  
Protein L ◽  
Cysteinyl Leukotriene ◽  
Proinflammatory Mediators

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.

Mast Cell Heterogeneity in Human Lung Tissue

1989 ◽  
Vol 77 (3) ◽  
pp. 297-304 ◽  
Author(s):  
F. J. Van Overveld ◽  
L. A. M. J. Houben ◽  
F. E. M. Schmitz du Moulin ◽  
P. L. B. Bruijnzeel ◽  
J. A. M. Raaijmakers ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Alcian Blue ◽  
Lung Tissue ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Human Lung Tissue ◽  
No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

scholarly journals Substance P can stimulate prostaglandin D2 and leukotriene C4 generation without granule exocytosis in murine mast cells

2004 ◽  
Vol 489 (1-2) ◽  
pp. 49-54 ◽  
Author(s):  
Khalil Karimi ◽  
Mirjam Kool ◽  
Frans P. Nijkamp ◽  
Frank A. Redegeld
Keyword(s):  
Mast Cells ◽  
Substance P ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Granule Exocytosis

scholarly journals IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, beta-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells.

1983 ◽  
Vol 157 (1) ◽  
pp. 189-201 ◽  
Author(s):  
E Razin ◽  
J M Mencia-Huerta ◽  
R L Stevens ◽  
R A Lewis ◽  
F T Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Chondroitin Sulfate ◽  
Specific Antigen ◽  
Antigen Challenge ◽  
Prostaglandin D2 ◽  
Mouse Bone Marrow ◽  
Leukotriene C4 ◽  
Chondroitin Sulfate E

Mouse bone marrow-derived mast cells differentiated in vitro and sensitized with monoclonal IgE respond to antigen-initiated activation with the release of histamine, beta-hexosaminidase, chondroitin sulfate E proteoglycan, and leukotriene C4 (LTC4). The chondroitin sulfate E nature of the glycosaminoglycan side chain was established by demonstrating that the chondroitinase ABC disaccharide digestion products were composed of equal quantities of 4-sulfated and 4,6-disulfated N-acetyl-galactosamine. The single immunoreactive sulfidopeptide leukotriene, released and quantitated with a class-specific antibody, was identified as LTC4 by its retention time on reverse-phase high-performance liquid chromatography and by its specific spasmogenic activity on the guinea pig ileum. The release of the preformed mediators, as well as of LTC4, was related in a dose-response fashion to the concentration of monoclonal IgE used during the sensitization step and to the concentration of specific antigen used to initiate the activation-secretion response. The optimal concentrations of IgE for sensitization and of antigen for challenge were the same for the release of preformed mediators and of LTC4. In addition, the time courses of their release were superimposable, with a plateau at 5 min after antigen challenge. The release of three preformed mediators and of LTC4 after fixation of IgE, washing of the sensitized cells, and antigen challenge unequivocally indicates a bone marrow-derived mast cell origin for these products. Linear regression analyses of the net percent release of beta-hexosaminidase to histamine and of 35S-chondroitin sulfate E to beta-hexosaminidase yielded straight lines that intersected at the origin, which indicates that the three preformed mediators are localized in the secretory granules of the bone marrow-derived mast cells. The concomitant generation of 23 ng of LTC4/10(6) sensitized bone marrow-derived mast cells represents the first example of IgE-dependent release of substantial amounts of LTC4, a component of slow reacting substance of anaphylaxis, from a mast cell population of greater than 95% purity. The IgE-dependent generation of LTC4, rather than prostaglandin D2, by the chondroitin sulfate E proteoglycan-containing bone marrow-derived mast cells contrasts with the predominant generation of prostaglandin D2 by heparin proteoglycan-containing mast cells. These differences together support the existence of two phenotypically different mast cell subclasses.

The relationship of IGE receptor topography to signaling activity in RBL-2H3 mast cells

1991 ◽  
Vol 49 ◽  
pp. 236-237
Author(s):  
J.R. Pfeiffer ◽  
J.C. Seagrave ◽  
C. Wofsy ◽  
J.M. Oliver
Keyword(s):  
Mast Cells ◽  
Protein A ◽  
Scattered Electron ◽  
Ige Receptor ◽  
Receptor Complexes ◽  
Ige Binding ◽  
Electron Imaging ◽  
Small Clusters ◽  
Relationship Of ◽  
The Relationship

In RBL-2H3 rat leukemic mast cells, crosslinking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor crosslinking also stimulates the redistribution of receptors on the cell surface, a process that can be observed by labeling the anti-IgE with 15 nm protein A-gold particles as described in Stump et al. (1989), followed by back-scattered electron imaging (BEI) in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37“C from a dispersed topography (singlets and doublets; S/D) to distributions dominated sequentially by short chains, small clusters and large aggregates of crosslinked receptors. These patterns can be observed (Figure 1), quantified (Figure 2) and analyzed statistically. Cells incubated with 1 μg/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors as far as chains and small clusters during a 15 min incubation period. At 3 and 10 μg/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates.

Design of peptide affinity ligands for S-protein: a comparison of combinatorial and de novo design strategies

2013 ◽  
Vol 17 (2) ◽  
pp. 357-369 ◽  
Author(s):  
Divya Chandra ◽  
Christopher J. Morrison ◽  
James Woo ◽  
Steven Cramer ◽  
Pankaj Karande
Keyword(s):  
De Novo ◽  
Protein A ◽  
De Novo Design ◽  
Design Strategies ◽  
S Protein ◽  
Affinity Ligands ◽  
Peptide Affinity

scholarly journals Ultrastructural Studies of Human Basophils and Mast Cells

2005 ◽  
Vol 53 (9) ◽  
pp. 1043-1070 ◽  
Author(s):  
Ann M. Dvorak
Keyword(s):  
Growth Factor ◽  
Mast Cells ◽  
Cord Blood ◽  
Blood Cells ◽  
De Novo ◽  
Ultrastructural Studies ◽  
Specific Growth Factor ◽  
Cord Blood Cells ◽  
Human Basophils

Ultrastructural studies of human mast cells (HMCs) and basophils (HBs) are reviewed. Sources of HMCs include biopsies of tissue sites and in situ study of excised diseased organs; isolated, partially purified samples from excised organs; and growth-factor-stimulated mast cells that develop de novo in cultures of cord blood cells. Sources of HBs for study include partially purified peripheral blood basophils, basophils in tissue biopsies, and specific growth factor-stimulated basophils arising de novo from cord blood cells. The ultrastructural studies reviewed deal with identity, secretion, vesicles, recovery, and synthesis issues related to the biology of these similar cells.

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