Opioid-Induced Mast Cell Activation and Vascular Responses Is Not Mediated by ??-Opioid Receptors: An In Vivo Microdialysis Study in Human Skin

Exposure to ambient ozone (O3) is associated with increased exacerbations of asthma. We sought to determine whether mast cell degranulation is induced by in vivo exposure to O3in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O3. For this we exposed mast cell-deficient WBB6F1- kitW/ kitW-v( kitW/ kitW-v) mice and the congenic normal WBB6F1(+/+) mice to air or to 1 or 3 parts/million O3for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/milllion O3only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kitW/ kitW-vand +/+ mice after exposure to O3. Thus, although mast cells are activated in vivo by O3and participate in O3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O3-induced airway hyperresponsiveness in mice.

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The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function.

Journal of Experimental Medicine ◽

10.1084/jem.175.1.245 ◽

1992 ◽

Vol 175 (1) ◽

pp. 245-255 ◽

Cited By ~ 88

Author(s):

B K Wershil ◽

M Tsai ◽

E N Geissler ◽

K M Zsebo ◽

S J Galli

Keyword(s):

Mast Cell ◽

Stem Cell ◽

Mast Cells ◽

Stem Cell Factor ◽

Cell Activation ◽

Mast Cell Activation ◽

Tyrosine Kinase Receptor ◽

Kit Ligand ◽

Kit Receptor

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.

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Delta opioid receptors regulate calcium-dependent, amphetamine-evoked glutamate levels in the rat striatum: an in vivo microdialysis study

Brain Research ◽

10.1016/s0006-8993(00)02030-8 ◽

2000 ◽

Vol 861 (2) ◽

pp. 296-304 ◽

Cited By ~ 42

Author(s):

Scott M Rawls ◽

Jacqueline F McGinty

Keyword(s):

Opioid Receptors ◽

In Vivo Microdialysis ◽

Rat Striatum ◽

Calcium Dependent ◽

Delta Opioid Receptors ◽

Microdialysis Study

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Increased Severity of Local and Systemic Anaphylactic Reactions in Gp49b1-Deficient Mice

Journal of Experimental Medicine ◽

10.1084/jem.194.2.227 ◽

2001 ◽

Vol 194 (2) ◽

pp. 227-234 ◽

Cited By ~ 53

Author(s):

Massoud Daheshia ◽

Daniel S. Friend ◽

Michael J. Grusby ◽

K. Frank Austen ◽

Howard R. Katz

Keyword(s):

Mast Cell ◽

Cell Activation ◽

Mast Cell Activation ◽

Critical Question ◽

Increased Sensitivity ◽

Antibody Levels ◽

Deficient Mice

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcεRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

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IgE Enhances Mouse Mast Cell FcεRI Expression In Vitro and In Vivo: Evidence for a Novel Amplification Mechanism in IgE-dependent Reactions

Journal of Experimental Medicine ◽

10.1084/jem.185.4.663 ◽

1997 ◽

Vol 185 (4) ◽

pp. 663-672 ◽

Cited By ~ 295

Author(s):

Masao Yamaguchi ◽

Chris S. Lantz ◽

Hans C. Oettgen ◽

Ildy M. Katona ◽

Tony Fleming ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Immunoglobulin E ◽

Specific Antigen ◽

Mast Cell Activation ◽

Proinflammatory Mediators ◽

Mouse Mast Cell

The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεRI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of FcεRI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell FcεRI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.

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