Leukotriene c4

Like LTD4 and LTE4, the inflammatory, unstable leukotriene C4 (LTC4) belongs to the cysteinyl leukotrienes and has a direct, leukocyte-independent, increasing effect on the permeability of postcapillary venules of various vascular regions. Leukotriene C4 is produced by neutrophilic and basophilic granulocytes, mast cells and mononuclear phagocytes in response to acting inflammatory mediators. It is synthesized by coupling glutathione to leukotriene A4 which acts as an intermediate.

Leukotriene C4 (LTC4) is a leukotriene that plays a role in allergic diseases, especially bronchial asthma.

All cysteinyl leukotrienes bind with different affinity to 2 G-protein bound receptors: CYSLTR1 and CYSLTR2 (CYSLTR = acronym for "cysteinyl leukotriene receptor"). These 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.

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

Furthermore, LTC4 and LTD4 have a strong vasoconstrictive effect on the coronary arteries. Likewise, the smooth muscles of the gastrointestinal tract are contractively excited by the cysteinyl leukotrienes.

In animal experiments, the cysteinyl leukotrienes lead to a disturbance of the microcirculation of the mucosa of the stomach. The substances thus potentiate the effect of other noxious agents.

Blocking the CYSLTR1 and CYSLTR2 receptors by leukotriene receptor antagonists (e.g. zafirlukast, montelukast) have a beneficial antiasthmatic effect. Montelukast binds to the CYSLTR1 receptors and thus prevents the effects of cysteinyl leukotrienes with regard to inflammatory action and increased mucus secretion.

LTC4 induces nuclear translocation of NADPH oxidase 4 (NOX4) and oxidative DNA damage via accumulation of ROS.

LTC4 is involved in various diseases. diseases such as allergic respiratory and skin diseases, cardiovascular and hepatic diseases, arteriosclerosis and colon cancer.

1. Al-Azzam N et al (2015) Modulation of mast cell proliferative and inflammatory responses by leukotriene d4 and stem cell factor signaling interactions. J Cell Physiol 230:595-602.
2. Chen LY et al (2011) Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes. Allergy 66:1304-1311.
3. Guan WJ et al (2015) Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study. Clin Respir J 9:111-120.
4. Kondeti V et al (2016) Leukotriene D4 and prostaglandin E2 signals synergize and potentiate vascular inflammation in a mast cell-dependent manner through cysteinyl leukotriene receptor 1 and E-prostanoid receptor 3 J Allergy Clin Immunol 137:289-298.