Histamine

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Histamine

WHAT IS HISTAMINE?

Histamine is an important protein involved in many allergic reactions. Allergies are caused by an immune response to a normally innocuous substance (i.e. pollen, dust) that comes in contact with lymphocytes specific for that substance, or antigen. In many cases, the lymphocyte triggered to respond is a mast cell. For this response to occur, a free-floating IgE (an immunoglobulin associated with allergic response) molecule specific to the antigen must first be attached to cell surface receptors on mast cells. Antigen binding to the mast cell-attached IgE then triggers the mast cell to respond. This response often includes the release of histamine (Janeway et al 1999).

                                   Fig. 1. Histamine bound to carbonic anhydrase II
                                Permission to use requested (See Protein Data Bank)

WHAT DOES HISTAMINE DO?

The release of histamine (hist = because it's made up of histidine residues, amine = because it's a vasoactive amine) causes several allergic symptoms. 1) It contributes to an inflammatory response. 2) It causes constriction of smooth muscle.

Histamine can cause inflammation directly as well as indirectly. Upon release of histamine by an antigen activated mast cell, permeability of vessels near the site is increased. Thus, blood fluids (including leukocytes, which participate in immune responses) enter the area causing swelling. This is accomplished due to histamine’s ability to induce phosphorylation of an intercellular adhesion protein (called (VE)-cadherin) found on vascular endothelial cells (Andriopoulou et al 1999). That is why histamine is known as being vasoactive. Gaps between the cells in vascular tissue are created by this phosphorylation, allowing blood fluids to seep out into extracellular space. Indirectly, histamine contributes to inflammation by affecting the functions of other leukocytes in the area. It has been suggested by Marone et al that histamine release triggers the release of cytokines and inflammatory mediator by some neighboring leukocytes (1999). These chemicals in turn increases the inflammatory response.

Histamine's second type of allergic response is one of the major causes for asthma. In response to an allergen (a substance that triggers an allergic reaction), histamine, along with other chemicals, causes the contraction of smooth muscle (Schmidt et al 1999). Consequently, the muscles surrounding the airways constrict causing shortness of breath and possibly complete trachial-closure, an obviously life-threatening condition. If the effects of histamine during an allergic reaction are inhibited, the life of an allergic person can be eased (in the case of inflammation) or even saved by preventing or shortening asthma attacks. Thankfully, many effective drugs have been developed to hinder histamine's allergic response activities.

Antihistamines

Allergies are frequently treated by drugs called antihistamines (because they inhibit the activity of histamine). Some contemporary examples are Claritin and Allegra, but antihistamines have been in use since as early as the 1930s and they continue to be an effective way to deal with the problems of allergies (Emanuel 1999). One effect antihistamines have is the inhibition of the histamine-mediated release of inflammatory mediators by leukocytes (Cuss 1999). Other antihistamine effects result in the neutralization of histamine, preventing it from binding and activating immune-related cells in the area. An allergic reaction is an immune response that should not be occurring because the substance that triggers it should not be dangerous to us. Allowing our immune system to run its course against allergens means living with annoying and potentially dangerous symptoms. The use of antihistamines allows us to live more safely and comfortably by counteracting the body's immunological mistakes.

References

Andriopoulou P, Navarro P, Zanetti A, Lampugnani MG, Dejana E. 1999 Oct. Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arteriosclerosis Thrombosis and Vascular Biology 19(10): 2286-2297.

Cuss FM. 1999 July. Beyond the histamine receptor: effects of antihistamines on mast cells. Clinical and Experimental Allergy 29: 54-59.

Emanuel, MB. 1999 July. Histamine and the antiallergic antihistamine: a history of their discoveries. Clinical and Experimental Allergy 29: 1-11.

Janeway CA, Travers P, Walport M, Capra JD. Immunobiology: the Immune System in Health and Disease. 4th ed. London: Current Biology Publication; 1999. p 602.

Marone G, Granata F, Spadaro G, Onorati AM, Triggiani M. 1999. Antiinflammatory effects of oxatomide. Journal of Investigational Allergology and Clinical Immunology 9(4): 207-214.

Protein Data Bank. Structure Explorer - 1AVN. <http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1AVN> Accessed 2000 Mar 2.

Schmidt D, Ruehlmann E, Branscheid D, Magnussen H, Rabe KF. 1999 Aug. Passive sensitization of human airways increases responsiveness to leukotriene C4. European Respiratory Journal 14(2): 315-319.

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