Activation Of Mast Cells In Tissues Research Articles

L’immunothérapie spécifique agit-elle sur l’immunité innée ?

Specific immunotherapy (SIT), whether it be subcutaneous or sublingual, relies upon several intricate antigen-specific immune mechanisms, including the modulation of CD4 + T cell responses (stimulation of Th1 and T Reg responses), as well as the induction of anti-inflammatory “blocking” antibodies (IgG4 or IgA). The impact of SIT on innate immunity (i. E. , antigen-independent) has yet to be investigated, but may encompass a direct effect on epithelial cells, dendritic cells (DCs), and/or mast cells and basophils. Mucous epithelial cells are the first to come in contact with allergen, and their response to this stimulus differs between allergic and non-allergic individuals. SIT has been reported to modulate the function of plasmacytoid DCs in the peripheral blood (with induction of IFNα secretion following stimulation with a TLR9 ligand), and the question is raised as to whether SIT can elicit a “tolerogenic” phenotype in DCs. With this in view, we are currently engaged in a proteomic study aiming to identify potential molecular markers of regulatory DCs. SIT appears to have an effect on the activation of tissue mast cells and circulating basophils (probably via regulation of activation signals). Nonetheless, our recent SLIT study in grass pollen allergic patients dœs not confirm a correlation between clinical efficacy and a decrease in circulating basophil activation.

Dexamethasone or cyclosporin A suppress mast cell-leukocyte cytokine cascades. Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous inflammation in the mouse.

In allergic diseases, exposure of sensitized subjects to allergen induces the activation of tissue mast cells that results in an immediate-type hypersensitivity response and, in some individuals, a a late phase response. We previously have reported that the neutrophil infiltration associated with IgE-dependent cutaneous inflammation in mice is mast cell-dependent and that TNF-alpha contributes significantly to this response. We report here that either dexamethasone or cyclosporin A can inhibit mouse mast cell TNF-alpha production in vitro, and that these agents also can significantly suppress the tissue swelling and leukocyte infiltration associated with two forms of TNF-alpha-associated inflammation in vivo: the entirely IgE- and mast cell-dependent inflammation at sites of passive cutaneous anaphylaxis reactions and the entirely TNF-alpha-dependent inflammation that is elicited by the direct intradermal injection of recombinant mouse TNF-alpha. Taken together, our in vitro and in vivo findings in mice indicate that dexamethasone or cyclosporin A can have at least three actions that interfere with the pathogenesis of IgE, mast cell, and cytokine-dependent inflammatory reactions:suppression of the IgE-dependent increase in TNF-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases.

Is contact activation of the coagulation system involved in the genesis of the first-use syndrome?

A number of mechanisms have been thought to be involved in the pathogenesis of the first-use syndrome. These include IgE antibody-mediated response to ethylene oxide-related antigens, membrane activation of the alternative complement pathway, activation of tissue mast cells and basophils by materials released from the dialyzer into the circulation, and transfer of bacterial products through high flux dialyzer. However, the possible role of the activation of blood coagulation system and platelets during dialysis has not been considered. The present communication reviews the theoretical basis for a possible connection between dialysis-induced activation of platelets and coagulation system with the first-use syndrome. Although the available data concerning the activation of intrinsic coagulation pathway during dialysis are conflicting, there is no controversy as to the occurrence of platelet activation. It is suggested that biochemical events triggered by activation of these systems may in part contribute to the genesis of first-use syndrome.