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Abstract
Basophils are granulocytes, that constitute 0.4% of
leukocytes in circulating blood. They develop from CD34+
pleuripotential stem cells, differentiate and mature in the bone
marrow, then circulate in the periphery. IL-3 is the dominant
cytokine driving basophil differentiation.
Basophils express a complete and functional FcεRI (αβγ2),
cross-linking of which, leads to basophil activation, granule
exocytosis, and mediator release. C3a and C5a also activate
basophils through specific receptors. Activation through any of
these receptors leads to release of a spectrum of mediators,
including histamine, leukotriens, IL-4, IL-IL-13, and also minor amounts of IL-3, IL-25, and IL-17F.
Additional mediators such as, CC chemokines & RANTES, IL-3, IL-5, GM-CSF and histamine releasing factor, do not directly cause basophil mediator release-production but potentiate FcεRI effects.
Basophils participate in a wide range of human diseases, that includes:
a) Allergic inflammations; where they are recruited to allergic lesion sites, secrete histamine, express both IL-4 and IL-13 and have a role in anaphylaxis by secreting platelet activating factor (PAF).
b) Innate immune responses; basophils are activated by certain glycoproteins in some viruses and parasites, and also certain proteoglycans of some gram positive bacteria.
c) Delayed type hypersensitivity; basophils infilterate lesion sites along with eosinophils and mononuclear cells and become activated to release their mediators which results in the prolonged response known as cutaneous basophilic hypersensitivity (CBH).
Numbers of blood basophils have been altered in a variety of systemic disorders. Diseases associated with basophilia include allergy, inflammations, infections, endocrinopathies as well as various neoplasias. These neoplasias include basophilic leukemia, myeloproliferative diseases such as, chronic myeloid leukemia, polycythemia vera and primary thrombocythemia. Basophilopenia has been recorded in association with elevated levels of glucocorticoides, hyperthyroidism and some hypersensitivity reactions.
Mast cell is a tissue dwelling cell, that originate from CD34+ pleuripotent stem cells. Mast cell precursors circulate in the blood and home to tissues, where they mature under the influence of SCF produced by stromal cells, including fibroblasts and endothelial cells. Mast cell phenotype and behavior is altered by cytokines, such as IL-4, IL-5, and INF-γ. For example, IL-4 upregulates FcεRI expression, IL-5 promotes proliferation in the presence of SCF, and INF-γ decreases mast cell numbers.
Mast cell is being activated via FcεRI, also by C3a and C5a, nerve growth factor, and IgG. Mast cell mediators are divided into preformed mediators, newly synthesized lipid mediators, and cytokines.
Preformed mediators are packed within secretory granules and released upon activation, their principal constituents are histamine, proteases (tryptase and chymase), carboxypeptidase A, and proteoglycans (heparin and chondroitin sulfate E).
Lipid mediators include prostaglandin PGD2, leukotriene LTC4, leukotriene LTD4, and leukotriene LTE4.
Cytokines produced by mast cells include TNF-α, IL-4, IL-3, GM-CSF, IL-5, IL-6, IL-8, and IL-16. Human mast cells also produce chemokines, such as CCL3.
Mast cell participates in human diseases that include:
a) Allergic inflammation: mast cell activation occurs in type I hypersensitivity reaction, as a result of binding of the allergen to the IgE antibodies bound to the FcεRI. Mast cells activation results in the release of a large number of proinflammatory, immunoregulatory and tissue regulatory mediators.
b) Immune responses: mast cells are effector cells that elicit protective immune responses against bacteria, parasites, viruses and fungi. In addition they have a role in modulating acquired immune responses by expressing several costimulatory/inhibitory adhesion molecules, antigen presentation, and by their products as histamine, IL-1β, and PGE2.
c) Diverse roles of mast cells: in tumors, angiogenesis, tissue remodeling, heart disease, autoimmune disorders, nervous system.
Disorders associated with increased mast cell population, include IgE hypersensitivity reactions, connective tissue disease, infections, as well as multiple neoplastic disorders. These disorders include lymphoproliferative disease, hematopoietic stem cell disease, mast cell leukemia and mastocytosis.
Discriminating benign and malignant disorders of basophils and mast cells is mandatory by using various diagnostic tools such as bone marrow and extra-cutaneous organ biopsy sections, serum tryptase assessment, tryptase immunohistochemistry which is confirmatory for malignancy, c-kit mutation detection in bone marrow, and immunophenotyping.