Leukotriene e4

Leukotriene E4 (LTE4) is an inflammatory, stable end product of the 5-lipoxygenase metabolism of arachidonic acid. Leukotriene E4 (leukotriene: from Greek leukos =white and treis =three) is formed by neutrophil granulocytes and mononuclear phagocytes in response to acting inflammatory mediators.

LTE4 receptors: LTC4, LTD4 and LTE4 bind as cysteinyl leukotrienes with different affinity to 2 G-protein bound receptors: CYSLTR1 and CYSLTR2 (CYSLTR = acronym for "cysteinyl leukotriene receptor"), whereby the binding of LTE4 to these receptors is rather weak. The CYSLTR1/R2 receptors play an essential role in the endocrine and cardiovascular system. Mast cells and monocytes, among others, express this type of receptor. The stimulation of mast cells by LTD4 increases the c-kit induced proliferation of mast cells. It is possible that the GPR99 receptor expressed on eosinophilic granulocytes plays a specific role in the biological effects of LTE4.

Cysteinyl leukotrienes: The group of cysteinyl leukotrienes induces vasoconstriction and bronchoconstriction in the lung. In the bronchial muscles, this group of leukotrienes has a constrictive effect 1000 times stronger than histamine. They are important mediators in human bronchial asthma and allergic rhinitis.

Biosynthesis of LTE4: The biosynthesis of LTE4 is carried out in different synthesis steps via 5-HPETE, LTA4, LTC4, LTD4 and finally to the final product of the leukotrin synthesis pathway, LTC4. LTC4 is the most stable cysteinyl leukotriene. Compared to the short half-lives of LTC4 and LTD4, LTE4 can be detected in relevant concentrations in lung secretions, plasma and urine. Thus, LTE4 is an easily measurable biological parameter for monitoring leukotriene activity. In a larger study in infants and toddlers (age: 6-60 months) urine values of 619.73 ± 701.32 pg/ml were measured.

Production of leukotriene E4: Leukotriene E4 is produced by eosinophil and basophil granulocytes, mast cells, macrophages. Furthermore, the production is carried out by activated and aggregated thrombocytes.

Leukotriene levels: Elevated levels of LTE4 can be found in respiratory diseases, such as allergic bronchial asthma. LTE4 levels are elevated in patients with atopic diseases compared to control patients (642.20 ± 268/271.39 ± 83; cited in Marmarinos A et al.2015). LTE4 levels are significantly increased in aspirin-induced asthma (ASA intolerance syndrome or Samter's disease). LTE4 interacts synergistically with prostaglandins (PGD2) in the activation of Th2 cells, thereby increasing cytokine production. LTE4 has a weaker effect on bronchial muscles than LTD4, but has a particularly long-lasting effect due to its long half-life.

LTE4 and migraine: LTE4 levels are also found to be significantly elevated together with prostaglandin F2a in childhood migraine.

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