mast cells

Mast cells

Mast cells are regarded as one of the key cells of immune system of vertebrates. They are dispersed in most of the tissues but more common in locations which are exposed to the external environment  such as skin and mucosae. They are regulated by stem cell factor. Mast cells are specifically involved in protection from allergic diseases like asthama. These cells function by secreting chemical mediators which includes histamine, interleukins, proteoglycans (e.g heparin). Mast cells when stimulated release the contents of cytoplasmic granules in the neighbouring tissues, a process called degranulation that constitutes the allergic reaction. these cells are present in varying number throughout the body. mast cells and basophils are involved in the normal physiological counterpart hypersensitive reactions.

         Mast cells and basophils possess pharmacological materials and various enzymes in the suspended granules present in the cytoplasm.these active substances have a role in protection from the infectious disease by attacking the parasire.





Mast cells mediators

These cells expressed a variety of mediators and de novo secretions such as cytokine TNF? which acts as both preformed and newly synthesized.

Mast cells mediators are present in the secretory granules which upon stimulation release their products  in the surrounding tissues within minutes. These mediators include growth factors, proteases, leukotrienes, cytokines, and chemokines. Release of these mediators facilitates the actions of mast cells.

Several other factors are involved in the activation of mast cells. These include growth factors such as stem cell factor, co-stimulatory molecules CD28 (and ligands CD80/86), the integrins, and CCR1.these mediators are responsible for the physiological responses of mast cells.

Development          

Mast cells are the unique cells of innate immune reponse. These are produced as e result of hematopoiesis and are immaturely released into the circulating blood as progenitor. They get mature in the vascularized tissues. Usually 30000 to 50000 progenitors are present in per 35 ml of blood. Human mast cells possess a wide range of adhesion molecules and chemokine receptors that are involved in the regulation of mast cells.

Differentiation and maturation of mast cells is regulated by stem cell factor secreted by fibroblasts.. Human mast cells are matured by the action of interleukin (IL-4 IL-6 IL-10).matured mast cells have high proliferation rate. Mast cells are tissue specific and multifunctional cells. They are diversely distributed in the body therefore referred to as mast cell heterogeneity.

The mechanism of mast cells activation is well understood by IgE-Fc? cross linking 1[3] Binding of an antigen by Fc?RI-bound specific IgE leads to Fc?RI clustering which induces to release the mediators. many recent studies further explain the activation of mast cells through various complement pathways and patyern recognition receptors i.e toll like receptors, Nod-like receptors, C-type lectins such as Dectin-1, and the glycosylphosphatidylinositol-anchored protein CD48and many corticotrophin releasing hormones are also involved.4 5

Preformed mediators

Mast cells contain many preformed mediators present in the granules .These are released upon activation of the cell. Histamine is one of the preformed mediator. It has a role in allergic reactions.

Histamine 

Histamine is produced in the granules of mast cells and its mode of action is enhanced by basophils or neutrophils. Human cutaneous mast cells are estimated to contain 1.9 micrograms of histamine per 10(6) cells [3].The action of histamine is regulated by HI H2 H3 H4 receptors.

H1          effects include increased venular permeability, bronchial and          intestinal smooth muscle contraction, increased nasal mucus          production.in mice H1 is responsible for lung inflammation.

         H2          is mediated by H2 receptor and its effects include increased venular          permeability, bronchial and intestinal smooth muscle contraction,          increased nasal mucus production,78

         H3          receptor is present in the brain and in the blood vessels of nasal           mucosa and its role is still not characterised well.9  10

         H4          receptor modulates Th2 responses. H4 provides a chemotactic activity          for eosinophils.14

Function of  Mast Cells

Role of mast cells in allergic reactions

Paul Ehrlich described the histochemical properties of human basophils and mast clls.mast cells are activated by an allergen that binds to serum IgE attached to their Fc?RI receptors, they release cytokines and a process of degranulation starts.mast cells are thought to have role proinflammation due to the release of various mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases.







Mast cells in renal inflammation and fibrosis

Mast cells are not frequent in number in kidney tissue. But they are highly increased in number renal disorder i.e tubulointerstitial nephritis associated with progressive fibrosis and renal failure. Mast cells accumulation results in decline in glomerular filterate.

Anaphylaxis

Anaphylaxis is a severe systemic reaction to allergens such as bee stings or drugs. In anaphylaxis increased degranulation of mast cells leads to vasodilation.

Autoimmunity

Mast cells are also having a role in the autoimmume diseases rheumatoid arthritis, bullous pemphigoid, and multiple sclerosis.



Reproductive disorders

Mast cells are located in the endometrium and involved in the release of mediators In males, mast cells are present in the testes and are increased in oligo- and azoospermia, with mast cell mediators directly suppressing sperm motility