The Vasculitides

© Dirk Biddle

1.7.1.3 Basophils and Mast Cells

Basophils and mast cells may be present in greater numbers in allergic reactions. Basophils are the smallest and least common of the circulating leucocytes (0.4-1.0%). Basophils act very much like mast cells except that they usually circulate in the blood stream whereas mast cells settle in connective tissues. Both are filled with toxic chemicals that can digest micro-organisms and both express the same high affinity for Fce receptors (FceRI) and can be triggered by antigen binding to IgE. Upon stimulation, basophils and mast cells release pre-formed inflammatory (anaphylactic) >mediators such as >bradykinin, heparin, serotonin, and histamine. They also release cytokines, including tumour necrosis factor alpha (TNF-α) and (IL-4), that can modulate adhesion molecules on endothelial cells. This helps basophils attach to the vascular endothelium before migrating into the tissue. Stimulation of basophils and mast cells also result in the production of newly-formed mediators such as prostaglandins and leucotrienes, both of which are potent mediators of physiological activity such as inflammation and anaphylaxis. Stimulation also causes basophils and mast cells to release proteolytic enzymes, metabolites of arachidonic acid that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells, and chemotactic factors which attract neutrophils and eosinophils, which in turn may be implicated in vascular damage.

back

----------------------

Anaphylactic: Pertaining to anaphylaxis.
As opposed to prophylaxis. A system or treatment that leads to damaging effects on the organism.
Now reserved for those inflammatory reactions resulting from combination of a soluble antigen with IgE bound to a mast cell that leads to degranulation of the mast cell and release of histamine and histamine like substances, causing localised or global immune reponses.
Results in an acute allergic reaction with shortness of breath, rash, wheezing, hypotension. (OMD

Mediator: An object or substance (such as an enzyme, hormone or a neuropeptide) by which some (chemical or biological) process is mediated. An intermediate agency, the third agent that connects, or also as in catalyst.
1. A structure of the nervous system that transmits impulses eliciting a specific response.
2. A chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle, or
3. A substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitised lymphocyte. (OMD)

Bradykinin: Vasoactive nonapeptide (RPPGFSPFR) formed by action of proteases on kininogens. Very similar to kallidin (which has the same sequence but with an additional N terminal lysine).
Bradykinin is a very potent vasodilator and increases permeability of post capillary venules, it acts on endothelial cells to activate phospholipase A2. It is also spasmogenic for some smooth muscle and will cause pain. (OMD)

Heparin: Sulphated mucopolysaccharide, found in granules of mast cells, that inhibits the action of thrombin on fibrinogen by potentiating antithrombins, thereby interfering with the blood clotting cascade. Platelet factor IV will neutralise heparin. (OMD)

Serotonin:A neurotransmitter and hormone (176 kD), found in vertebrates, invertebrates and plants. It is synthesised from the amino acid tryptophan by enterochromaffin cells in the gut and bronchi. It is metabolised to 5-HIAA in the liver and then excreted in the urine.
Serotonin is measured on a venipuncture specimen in cases of suspected carcinoid syndrome (where it will be elevated). The normal range is 101 to 283 ng/ml.
Acronym: 5-HT (OMD)

Histamine: Formed by decarboxylation of histidine. Potent pharmacological agent acting through receptors in smooth muscle and in secretory systems.
Stored in mast cells and released by antigen. (See hypersensitivity). Responsible for the early symptoms of anaphylaxis. Also present in some venoms. (OMD)

Cytokine: Substance produced by a leucocyte that acts upon another cell. Small proteins or biological factors (in the range of 5-20 kD) that are released by cells and have specific effects on cell-cell interaction, communication and behaviour of other cells. Not really different from hormones, but the term tends to be used as a convenient generic shorthand for interleukins, lymphokines and several related signaling molecules such as TNF (tumour necrosis factor alpha) and interferons. Generally growth factors would not be classified as cytokines, though TGF is an exception. Rather an imprecise term. Chemokines are a subset of cytokines. (OMD)

TNF-α: Tumor necrosis factor alpha is a multifunctional proinflammatory cytokine with effects on lipid metabolism, coagulation, insulin resistance, and endothelial function. It is produced primarily by activated macrophages. It is found in synovial cells and macrophages in the tissues.
It shares many properties with another cytokine - interleukin 1. It occurs in many inflammatory diseases and also as a response to endotoxins from bacteria (for example)

Endothelium: The layer of epithelial cells that lines the cavities of the heart and of the blood and lymph vessels and the serous cavities of the body. (OMD)

Prostaglandin: Any of various oxygenated unsaturated cyclic fatty acids of animals that are formed as cyclooxygenase metabolites especially from unsaturated fatty acids (as arachidonic acid) composed of a chain of 20 carbon atoms and that perform a variety of hormone-like actions (as in controlling blood pressure or smooth muscle contraction). (M+)

Anaphylaxis: As opposed to prophylaxis. A system or treatment that leads to damaging effects on the organism.
Now reserved for those inflammatory reactions resulting from combination of a soluble antigen with IgE bound to a mast cell that leads to degranulation of the mast cell and release of histamine and histamine like substances, causing localised or global immune reponses.
Results in an acute allergic reaction with shortness of breath, rash, wheezing, hypotension. (OMD)

Chemotaxis: Orientation or movement of an organism or cell in relation to chemical agents. (M+)
A response of motile cells or organisms in which the direction of movement is affected by the gradient of a diffusible substance.
Differs from chemokinesis in that the gradient alters probability of motion in one direction only, rather than rate or frequency of random motion. (OMD)