Basophils are relatively rare cells that make up less than 1 % of blood leukocytes and are thought to play a role in expelling certain parasites but also contribute to allergic diseases. They were discovered in 1891 by Paul Ehrlich who showed that these granulated cells display similar staining characteristics to mast cells. Like mast cells, basophils produce histamine, which is stored in granules  consisting of proteoglycans from which it is released following stimulation and causes inflammation. Although basophils share many other properties with mast cells, such as expressing high-affinity IgE receptors (FcεRI), evidence to date suggests these cells are derived from different myeloid progenitors in the bone marrow (which also lead to eosinophils)  and certain key functional differences though these vary depending on the species. Basophils are generated in the bone marrow from where they are released into the blood. Recent advances in immunostaining (e.g. using antibodies to basogranulin, a basophil-specific protein)  has now demonstrated that basophils invade other tissues, such as the lungs and skin, or migrate to lymph nodes, during allergic inflammation and parasitic infections [4,5].
Activation of basophils
Basophils can be activated by nanograms per liter concentrations of allergen following prior sensitization with allergen-specific IgE. Activation occurs by crosslinking of at least two (probably more) IgE-FcεRI complexes with allergen, triggering the phosphorylation of Lyn and Syk protein kinases which control subsequent activation of stimulatory signal transduction pathways which crucially involve the influx of calcium ions into basophils. Lyn is also associated with the initiation of inhibitory signaling pathways involving phosphatases like SHIP-1, which limits basophil activation .
There are a number of other stimuli that cause non-specific crosslinking of FcεRI-bound IgE, including the IPSE/alpha-1 present in Schistosoma mansoni eggs , HIV-1 gp120 , B cell superantigens , leading to the introduction of the term ‘superallergen’ , and dietary lectins . Stimulation of such IgE-dependent stimuli can be markedly enhanced by a number of priming cytokines, such as IL-3 , GM-CSF , NGF  and IL-33 , as well as chemokines such as eotaxin . IgE-independent activators of basophils include the gram positive bacterial peptide fMLP  as well as complement factors C5a  and C3a , which can also cause marked degranulation, TLR ligands (although these do not usually cause substantial histamine release) , and leukocyte immunoglobulin-like receptor (LIR)-7 . Basophil activation also results in the fast up-regulation of several surface activation markers (Table 1). These can be used for detection of basophil activation in basophil activation tests (BATs) in whole blood [22–24].
Degranulation of basophils results in the rapid release of histamine which usually occurs within 30 minutes of allergen stimulation (and more rapidly for fMLP). This is followed immediately by the production and release of the eicosanoid leukotriene C4 (but unlike mast cells basophils do not produce cyclooxygenase products such as prostaglandin D2) . Interestingly, basophils rapidly release IL-4 within 4 hours after IgE-dependent stimulation and IL-13 over longer periods [26,27]. Both cytokines play a central role in supporting late-phase allergic reactions (by upregulating vascular adhesion molecules) and pro-allergic Th2 immunity. It is thought that basophils are the main early source of these cytokines whereas human mast cells are poor producers of these factors, especially IL-4. They have also been reported to release VEGF , a factor involved in angiogenesis and tissue remodelling.
Role of basophils in allergy and parasite immunity
Although basophils are usually found in the circulation and are rarely present in normal tissues, they have been widely shown to invade allergic inflamed sites in allergic individuals. Basophils express various chemokine receptors (see Table 2 for a selection) and respond to many chemotactic agents which aid their migration. Activation of basophils in allergic inflammatory sites has been demonstrated by differential mediator analysis, indicating that basophils and not mast cells do release their mediators in the late phase of the allergic response. Their presence in tissues affected by allergic disease, including in the airways of asthmatic patients, in the skin of atopic dermatitis patients, and in the nose has been demonstrated using basophil-specific BB1 and 2D7 antibodies [3,29]. In the rapid anaphylactic reactions following insect venom exposure, or food intake in food allergic patients, blood basophils and not so much tissue-resident mast cells have been hypothesized to play a role.
It is unlikely that basophils, with their clear potential to have detrimental effects, would have evolved and been widely preserved in higher animals without an important immune function. The first indications of such a role of basophils goes back to the pioneering work of William Trager, who demonstrated an essential involvement of basophils in immunity to hard ticks . A more refined understanding regarding the interplay between basophils and mast cells in tick infestation comes from the work of Hajime Karasuyama and his team . The role of basophil in immunity is not limited to exoparasites. A role for basophils in immunity to endoparasites (intestinal helminths) has been described by many authors since the pioneering work of Jarrett and Bazin . More recently, the availability of murine basophil knockout models has enabled researchers to dissect the roles of basophils in immunity to helminth parasites in greater detail [31,33]. It remains to be determined to which extent these findings can be extrapolated to human basophils [34–36].
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