Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: A possible role for mast cells in late-phase allergic reactions

Piliponsky, Adrian M.; Pickholtz, Dalia; Gleich, Gerald J.; Levi‐Schaffer, Francesca

doi:10.1067/mai.2001.114656

Cited by 70 publications

(52 citation statements)

References 43 publications

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“…Indeed, eosinophil-derived cationic proteins such as MBP have been reported to release prostaglandins from epithelial cells (50) and histamine from mast cells (43,53) and basophils (45). These mediators are known to induce pronounced sensitizing effects on pulmonary C-fiber afferents, elevating their sensitivities to various chemical and mechanical stimulations (15,22,34).…”

Section: Discussionmentioning

confidence: 99%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gu Q, Wiggers ME, Gleich GJ, Lee L-Y. Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins. Am J Physiol Lung Cell Mol Physiol 294: L544-L552, 2008. First published January 4, 2008 doi:10.1152/ajplung.00271.2007.-It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318 -1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 M, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked ϳ10 min after MBP and lasted for Ͼ60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-L-glutamic or poly-L-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e.g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions. major basic protein; eosinophil cationic protein; eosinophil peroxidase; airway inflammation; airway hypersensitivity ASTHMA IS CHARACTERIZED BY chronic airway inflammation associated with airway infiltration of various inflammatory cells, particularly the eosinophils (7). Activated eosinophils are known to secrete a number of cationic proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) (16). Previous studies have shown that intratracheal instillation of eosinophil-derived cationic proteins such as MBP induces bronchoconstriction and bronchial hyperresponsiveness in a number of animal species (9,17,21). Similar effects can also be induced by intratracheal administration of synthetic cationic proteins such as poly-Llysine (PLL) (10,24,46).Most of the sensory inputs arising from airways and lungs are conducted in vagus nerves and their branches. Cell bodies of these sensory nerves reside in two adjacent but distinct anatomic structures, the nodose and intracranial jugular ganglia. It is known that Ͼ75% of vagal bronchopulmonar...

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Section: Discussionmentioning

confidence: 99%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Eosinophil cross-talk is important in regulating the severity, duration, and outcome of the allergic response. Within this framework we demonstrated that human peripheral blood eosinophils induce IgE-desensitized rat peritoneal mast cells to release histamine (3). We previously reported that rat peritoneal mast cells enhance eosinophil survival in vitro by the induction of GM-CSF autocrine production (4,5).…”

Section: Uring Allergic Inflammatory Reactions Mast Cells and Eo-mentioning

confidence: 99%

Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release

Temkin¹,

Kantor²,

Weg³

et al. 2002

The Journal of Immunology

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114

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We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%, respectively, at an optimal concentration) but not by anti-stem cell factor, anti-TNF-α, or anti-IFN-γ neutralizing Abs or by the antihistamine drugs pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD 98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8 release. Tryptase caused phosphorylation of extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot). Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA). Eosinophils were found to express proteinase-activated receptor 2 (FACS). When eosinophils were incubated with tryptase in the presence of anti-proteinase-activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8 release occurred. In summary, we have demonstrated that the preformed mast cell mediator tryptase induces cytokine production and release in human peripheral blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.

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“…MBP is cytotoxic to both mammalian cells and parasites, and its deposition onto tissues is associated with their dysfunction in a number of diseases (1,2). MBP also stimulates, in a non-cytotoxic manner, activation of neutrophils and release of histamine from basophils and mast cells (3)(4)(5)(6). The mechanism underlying the cytotoxic and cytostimulatory functions of MBP is unknown.…”

Section: The Eosinophil Major Basic Protein (Mbp)mentioning

confidence: 99%

“…5). The eight basic residues within this region (Arg-170, 3 Arg-193, His-196, Arg-203, Arg-208, Arg-209, His-211, and Arg-214) have been suggested to be responsible for MBP GAG binding based on the positions of bound sulfate groups in the crystal structure of MBP and on interactions observed in MBP crystals soaked with heparin disaccharide (12,13). His-196, Arg-208, and Arg-209 also correspond to the positions of conserved calcium-ligating residues in other CTLs (13).…”

Section: Pro-mbp Binds To the Surface Of 293t Cells-mbp Has Beenmentioning

confidence: 99%

“…There is no evidence that circulating pro-MBP is proteolytically processed. Intriguingly, pro-MBP isolated from pregnancy serum is substituted with a GAG chain, possibly a heparan sulfate type, covalently bound to Ser-62 3 of the propiece (20). It has therefore also been proposed that, in addition to the neutralizing effect of the acidic propiece, the pro-MBP GAG interacts with the CTL ligand-binding region and inhibits its function (13).…”

Section: The Eosinophil Major Basic Protein (Mbp)mentioning

confidence: 99%

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The Proform of the Eosinophil Major Basic Protein Binds the Cell Surface through a Site Distinct from Its C-type Lectin Ligand-binding Region

2006

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The highly basic eosinophil major basic protein (MBP), present in the crystalloid core of eosinophil leukocyte granules, has both cytotoxic and cytostimulatory properties and is directly implicated in a number of diseases. The crystal structure of MBP resembles that of the C-type lectin (CTL) superfamily, and recent data showed that MBP binds heparan sulfate glycosaminoglycan (GAG), with the CTL ligand-binding region as the binding site. MBP is synthesized as a proform (pro-MBP) containing an acidic propiece believed to neutralize the basic MBP domain. Using flow cytometry and site-directed mutagenesis, we demonstrate here that the MBP domain of pro-MBP binds to heparan sulfate GAG on the cell surface and that this is independent of GAG covalently bound to pro-MBP. Eight basic residues located in the CTL ligand-binding region of MBP were hypothesized previously to mediate GAG binding, but we found that surface binding was not compromised by the substitution of these residues with alanine. However, the analysis of a series of mutants with surface-exposed residues substituted with alanine showed that Ser-166, Arg-168, and Arg-171 are involved in surface binding. A binding site formed by these residues is located in the MBP domain between loop 1 and ␤-strand 5, outside the CTL ligand-binding region. The binding of a cell-surface heparan sulfate proteoglycan may be important in MBP action, and our findings suggest that two regions shown previously to contain the cytotoxic and cytostimulatory properties of MBP are accessible for ligand interaction in cell surface-bound MBP.

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Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: A possible role for mast cells in late-phase allergic reactions

Cited by 70 publications

References 43 publications

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release

The Proform of the Eosinophil Major Basic Protein Binds the Cell Surface through a Site Distinct from Its C-type Lectin Ligand-binding Region

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