Tissue: generic

Source: Biological Process

NodeType: Pathway

Notes: Headnote: Basophils belong to a subtype of leukocytes that contain granules known as granulocytes. There are very few basophils in blood which account for less than 1% of all leukocytes. Moreover, there are virtually no basophils in a healthy organism since they appear as a response to disorders generally caused by allergic reactions. Signaling description: Basophils, the largest granulocytes, are very similar to mast cells and originate from the same precursor. The activation of basophils, similarly that of mast cells, is primarily characterized by degranulation and the release of heparin, histamine, and leukotrienes from granules which leads to immediate hypersensitivity reactions. Unlike mast cells, basophils are introduced into blood in a mature state, so their effects are faster than those of mast cells. Unlike mast cells, basophils express MHC class II and co-stimulatory molecules which can transmit haptens and peptide antigens to Th2 cells and therefore stimulate their differentiation. Similarly to mast cells, which also express the high-affinity IgE receptor FCERI, basophils release inflammatory mediators such as histamine and LTC4 in response to IgE-mediated activation. FCER1 is expressed on mast cells and basophils as tetramers (FCER1A/MS4A2/2 of FCER1G). Antigen binding to IgE cross-links two FCERI leading to LYN phosphorylation. The multi-molecular complex, which includes GRAP2, LCP2, PLCG, and VAV1, form on LAT. FCERI aggregation induces PI3K, MAPK1, MAPK8, NF-kB, PLC, and PKC activation. An increase in calcium (Ca2+) also leads to the synthesis of arachidonic acid and lysophospholipid that support the fusion of mast cell granules with the membrane and release of their contents. In addition to the well-characterized ability of basophils to be activated by antigen-IgE complexes, basophils have also been shown to become activated by the IgD antibody class. IgD is a class of antibodies that is produced during the early phases of B-cell development, but its biological functions remain poorly defined. IL3, the key cytokine that activates the maturation of basophils, appears to have a prominent pro-survival effect on basophils that are influenced by the kinase PIM1. IL3 also enhances the production of IL4 and IL13 by basophils in response to IgE-mediated activation. In basophils, IL4 and IL13 production is also induced by TLR2-related signaling. IL18 and IL33 are also specific to the activation of basophils. IL18 is produced by macrophages, Kupffer cells, and mast cells and is associated with allergic disease and immunity to helminth parasites. In human basophils, the role of IL18 in basophil activation is not well established. IL33 is expressed by dermal fibroblasts, airway epithelial cells, and bronchial smooth muscle cells and is associated with IL4, IL13, and IL6. In addition, human basophils express the complement receptors CR1, CR3, CR4, and C5AR1. Outcome effects: Human basophils produce histamine in response to the complement component C5a in an IgE-independent manner. Basophils are known to contribute to allergic responses by inducing smooth muscle contraction once they migrate to the area of inflammation during the late phase response. Leukotrienes LTC4, LTD4, and LTE4 are smooth muscle constrictors. Like mast cells, basophils synthesize large amounts of cytokines, growth factors, and proinflammatory mediators. Most basophil-specific mediators include IL13, IL6, IL4, TNF, CD80, CD40, and TSLP. In the absence of pro-survival factors, neutrophils, eosinophils, and basophils all die by intrinsic apoptosis within a short time following maturation.

Description: Basophils belong to a subtype of leukocytes that contain granules known as granulocytes. Pathway is built manually using published studies.

Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-2dcb1e91-f90d-4fcb-9e85-59d5157f8f93