Basophil cytokine production

Schroeder JT, MacGlashan DW Jr. Lichtenstein LM Human basophils mediator release and cytokine production. Adv Immunol 2001 77 93-122. 

The studies of mast cell cytokine production described above have shown that maximal induction of cytokine synthesis and release usually occurs in response to IgE-dependent activation. In common with many cell types, there is evidence that FccRI on mast cells is coupled to the phospholipase C effector system that controls two distinct signal transduction pathways, one regulated by Ca " ions and the other by protein kinase C (PKC). Exocytotic degranulation is associated with an increased cytoplasmic level of Ca ions, and activation of mast cells can be therefore achieved by the use of calcium iono-phores which raise intracellular calcium concentrations through a receptor-independent mechanism. Alternative mast cell stimuli include phorbol-12-myristate-13-acetate (PMA) which activates PKC and induces mediator secretion from basophils and rodent mast cells but not from human mast cells, and concanavalin A (Con A), a lectin which can stimulate mast cells by cross-linking of cell-bound IgE and/or cell surface glycoproteins. 

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

Promotes chemotaxis and granule release by neutrophils, basophils, T cells Mitogenic for myeloid cells, supports antigen-independent growth of helper T cells Inhibits interferon secretion, induces thymocyte proliferation in presence of other IL s, inhibits Thl cytokine production Induction of synthesis of acute phase proteins, enhances stimulation of hematopoietic cell proliferation by IL-3 and T-cell development of B cells Activates NK cells, stimulates production of IFN-a by Thl cells... 

Topical tacrolimus suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during the initial skin immune response [97]. The inhibitojy effect of tacrolimus on the production of cytokines in T cells has been demonstrated in both Thl and Th2 cells [98]. This is coincident with reports that the transcription factor NEAT, a target for the calcium-regulated phosphatase calcineurin, mediates transcription of both Thl- and Th2-derived cytokines [99]. The effects of tacrolimus on other inflammatory cells such as skin mast cells, basophils, eosinophils, and Langerhans cells have also been studied extensively. Tacrolimus has been shown to inhibit histamine release and cytokine production from human skin, lung, and cord blood-derived cultured mast cells [100-102]. Tacrolimus has also been reported to have a direct inhibitory activity on eosinophil activation [103,104]. 

Tachimoto, H., Ebisawa, M., Kimata, M., Mori, K., likura, Y, and Saito, H. (1997). Effect of immunosuppressive drugs on cytokine production from cultured human mast cells and basophils. J. Allergy Clin. Immunol. 99 (Part 2), S123. 

Gain SJ, Gordon JR, Wershil BK. Cytokine production by mast cells and basophils. Curr Opinion Immunol 1991 3 865-872. 

Fig. 3. Th2 cells provide cytokines such as IL-4, IL-5, IL-9 and IL-13, which are essential for differentiation, survival and activity of basophils, mast cells and eosinophils. IL-4 and IL-13 induce IgE production from B cells. IL-5 induces eosinophils, increases eosinophil survival and reduces apoptosis. IL-9 stimulates mast cells. 

IL-18 also induces IL-4, IL-10 and IL-13 production, increases IgE expression on B cells and in association with IL-2, it enhances stimulus-induced IL-4 production from TH2 cells. Bone marrow-derived basophils produce IL-4 and IL-13 in response to a stimulus from IL-18 and IL-3. IL-18 in combination with IL-12 induces IFN-y from dendritic cells and bone marrow-derived macrophages. Adhesion molecules, ICAM-1 and VCAM-1, are induced by this cytokine on synovial fibroblasts and endothelial cells. It inhibits osteoclast formation via its induction of GM-CSF from T cells. The receptors ofIL-18, IL-18Ra and IL-18R(3, share their signaling mechanisms via the IL-1R family. Toll-like receptors also share the downstream signaling pathway of IL-18 and are known to regulate IL-18 expression. 

Olopatadine, in addition to its high affinity for the Hi receptor, has a lesser affinity for the H2 and Hj receptors. In in vitro studies the drug inhibits mast cell and basophil degranulation by greater than 90%. The mast cell-stabilizing properties olopatadine are less than those of cromolyn, nedocromil, or pemirolast. Olopatadine also inhibits the production of inflammatory cytokines. 

Once sensitivity has been established, that is, once hapten-specific IgE-producing B cells have been formed, exposure to even small amounts of hapten can induce a cascade of events that lead to immediate reactions, such as anaphylaxis (210). Briefly, preformed IgE antibodies to drug determinants recognize the hapten-carrier complex and fix to the surface of mast cells or basophils, triggering the release of a series of mediators, such as histamine, neutral proteases, biologically active arachidonic acid products, and cytokines. This ultimately leads to a clinical spectrum that ranges from a mUd local reaction to anaphylactic shock. 

A recent study by Brunner a al. (1993) has confirmed that mature human basophUs synthesize and release IL-4. For optimal secretion, priming with IL-3 for 18-48 h before activation with anti-IgE was required, although low amounts of IL-4 were occasionally detected following incubation with either IL-3 or anti-IgE alone. No spontaneous IL-4 production was detected, and other cytokines known to enhance basophil mediator release, namely IL-5, GM-CSF and nerve growth factor (NGF),... 

Seder, R.A., Paul, W.E., Ben Sasson. S.Z., LeGros, G.S., Kagey-Sobotka, A., Finkelman, F.D., Pierce, J.H. and Plaut, M. (1991a). Production of interleukin-4 and other cytokines following stimulation of mast cell lines and in vivo mast cells/basophils. Int. Arch. Allergy Appl. Immunol. 94, 137-140. 

Figure 22-7 summarizes the Th2 polarization, which usually occurs because of antigenic stimulation by allergens or extraceEular antigens like hehninthic (parasite) antigens. This stimulation is associated with a lack of IL-12 and IFNy production by APCs and the absence of NK activation. However, it is dependent on mast cells and basophils, which are involved in IL-4 synthesis. Thus there is an environment rich in IL-4 (increased by the spontaneous endogenous production of this cytokine) and poor in IFNy. 

IL-5 also enhances the expression of IL-2R on B cells and stimulates basophils. Proeosinophilic and/or proallergic Th2 cytokines, originally described as T lymphocyte products, have been ascribed to mast cells as weU, and these cells are probably analogous to T cells in the requirement of costimuli for the production of IL-5 protein. Moreover, the rapid kinetics of IgE-mediated IL-5 transcription and protein elaboration are consistent with a primary role for mast cell activation, directly leading to late phase airway eosinophilia. ... 

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