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Review
, 2016, 8232830

The Evolution of Human Basophil Biology From Neglect Towards Understanding of Their Immune Functions

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Review

The Evolution of Human Basophil Biology From Neglect Towards Understanding of Their Immune Functions

Markus Steiner et al. Biomed Res Int.

Abstract

Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Timeline of discoveries during the evolution of basophil research.
Figure 2
Figure 2
Influence of C/EBPα and GATA-2 on the basophil development in spleen (left) and bone marrow (right). In the final maturation step basophils might be either elicited by IL-3 or TSLP. HSC: hematopoietic stem cell; CLP: common lymphoid progenitor; CMP: common myeloid progenitor; GMP: granulocyte/monocyte progenitor; BMCP: basophil/mast cell progenitor; pre-BMP: prebasophil mast cell progenitor; BaP: basophil progenitor; IL-3: interleukin 3; TSLP: thymic stromal lymphopoietin.
Figure 3
Figure 3
Surface molecules (boxes) and secreted mediators (arrows) of human basophils. BAFF, B cell-activating factor; CxaR, anaphylatoxin receptors; CCL/CXCL, chemokine ligands; CCR, CXCR, chemokine receptors; CD, cluster of differentiation; CRTH2, chemoattractant receptor-homologous molecule expressed on TH2 cells; FcxR, immunoglobulin receptors; FPR, formyl peptide receptors; GM-CSFR, granulocyte macrophage colony-stimulating factor receptor; IL, interleukin; IL-R, interleukin receptor; LepR, leptin receptor; LIR, leukocyte immunoglobulin-like receptor; LTC4, leukotriene C4; MMP-9, matrix metallopeptidase; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PAF, platelet activating factor; SDF-1, stromal cell-derived factor 1; ST2, growth stimulation expressed gene 2; TLR, toll-like receptors; TNFα, tumor necrosis factor alpha; TRAIL-R, tumor necrosis factor-related apoptosis-inducing ligand receptor; Trk-A, tropomyosin receptor kinase A; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor; VEGF-A, vascular endothelial growth factor A.
Figure 4
Figure 4
Scheme of basophil activation via FcεRI cross-linking and the involved signaling pathways leading to mediator release. Basophil-derived IL-4 and IL-13 trigger Th2 responses and enhance immunoglobulin production from B cells. DAG, diacylglycerol; ERK, extracellular signal-regulated kinase; FcεRI, high affinity IgE receptor 1; Fyn, src-related proto-oncogene; IgE, immunoglobulin E; IL, interleukin; IP3, inositol trisphosphate; LTC4, leukotriene C4; Lyn, Lck/Yes novel tyrosine kinase; PI3K, phosphoinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; MEK, MAPK/ERK Kinase; Raf, rapidly accelerated fibrosarcoma; Ras, rat sarcoma; S1P, sphingosine-1-phosphate; SK, sphingosine kinase 1; Syk, spleen associated tyrosine kinase.
Figure 5
Figure 5
Determination of the hypoallergenic factor (here of 122) from C50 values of allergen (20.1 pg/mL, in red) versus hypoallergen (2.46 ng/mL, in blue). The experimentally determined activation values (⧫) have been approximated to analytically defined sigmoidal curves (broken lines) from which the C50 values were calculated [178].

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