Leucotriene b4

Leukotriene B4 (LTB4) is an inflammatory leukotriene (leukotriene: from Greek leukos =white and treis =three) formed by neutrophilic granulocytes and mononuclear phagocytes in response to acting inflammatory mediators. LTB4 is synthesized from LTD4 by the leukotriene A4 hydrolase, also known as LTA4H. The leukotriene A4 hydrolase is a bifunctional enzyme that on the one hand hydrolyses the unstable leukotriene A4 into leukotriene B4. On the other hand the enzyme acts as an aminopeptidase.

LTB4 acts chemotactically and chemokinetically, progaggregating and degranulating on leukocytes. The leukotriene is able to cause the adhesion and activation of leukocytes to the inner wall of the vessel. LTB4 has no direct effect on the permeability of vessels. However, after the adhesion of leukocytes to the endothelial cells, there is a strong local increase in vascular permeability, local edema and hyperalgesia.

On neutrophil granulocytes and mononuclear phagocytes LTB4 acts as a chemoattractant. Leukotriene activates these cells and induces oxygen radicals and the release of lysosomal enzymes.

LTB4 binds to 2 protein-G coupled transmembrane receptors, the high-affinity BLT1 receptor and the low-affinity receptor, BLT2. BLT1 is expressed by numerous cells, including type 1, type 2 and type 17 helper cells, CD8-positive lymphocytes, on eosinophilic granulocytes, macrophages, dendritic cells and osteoclasts.

Interleukin-23 (IL-23) is able to induce the synthesis and secretion of leukotriene B4 (LTB4), so that autocrine activation of LTB4 is possible via this pathway.

Leishmanicidal effect of LTB4: LTB4 is able to reduce the parasite load of macrophages infected with leishmania. This LTB4 effect is accompanied by an increased secretion of Reactive Oxygen (ROS) by macrophages.

Arteriosclerosis: Leukotriene B4 together with the extracellular matrix metalloproteinase (MMP) plays a pathogenetic role in the instability of ateriosclerotic plaques. Serum levels of LTB4 are elevated in acute myocardial infarction. This phenomenon is accompanied by increased expression of MMP on monocytes.

Systemic scleroderma: The concentration of LTB4 and LTE4 serum levels is increased in the lavage fluid of patients with systemic scleroderma. This finding correlates with lung inflammatory parameters.

Inactivation of LTB4: Omega oxidation to 20-hydroxy or 20-carboxy derivatives is the main pathway of LTB4 inactivation.

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