Suppression of mast cell activation by glucocorticoid.
Mast cells play a critical role in allergic diseases. When mast cells are activated by cross-linking of their high affinity IgE receptors by the antigen and IgE antibodies, release of chemical mediators is followed by secretion of multiple cytokines. We report that IL-3-dependent mucosal-type mast cells undergo apoptosis when IL-3 is withdrawn. In addition, cross-linking of high affinity IgE receptors prevents apoptosis of mast cells by paracrine mechanisms, producing IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). However, the secretion of endogenous growth factors are not enough for cell survival, whereas IL-4 induces cell aggregation by expressing adhesion molecules such as leukocyte function-associated antigen 1 (LFA-1), and makes it reactive to endogenous growth factors by contact cell to cell interaction. On the other hand, dexamethazone down-regulates the expression of intracelluar adhesion molecule 1 (ICAM-1) and IL-4 in activated mast cells, by which the self-aggregation of mast cells is inhibited and apoptosis is induced. Thus, glucocorticoids suppress mast cell survival by inhibiting IL-4 production and expression of adhesion molecules.
Yoshikawa
H
H
Department of Parasitology and Immunology, Yamanashi Medical University, Japan.
Tasaka
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology; D015533:Transcriptional Activation / Q000187:drug effects
D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011965:Receptors, Glucocorticoid