A novel clade of cysteinyl leukotriene scavengers in soft ticks

• Published in: Insect biochemistry and molecular biology Vol. 38; no. 9; pp. 862 - 870
• Main Authors: Mans, Ben J., Ribeiro, José M.C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2008
• Subjects: AM-33; Amino Acid Sequence; Animals; Argas - genetics; Argas - metabolism; Argas monolakensis; Argasidae; Basophil; Biological Assay; Cysteine - metabolism; cysteinyl leukotriene scavengers; eicosanoids; Evolution, Molecular; Guinea Pigs; hematophagy; Hydrophobic and Hydrophilic Interactions; immune response; In Vitro Techniques; inflammation; Ixodidae; Leukotrienes; Leukotrienes - metabolism; Ligands; Lipocalins - genetics; Lipocalins - metabolism; Mast cell; Models, Molecular; Molecular Sequence Data; Ornithodoros savignyi; Phylogeny; Sequence Alignment; ticks; TSGP4; Vasodilator; Ornithodoros savignyi; Vasodilator; Leukotrienes; AM-33; Argas monolakensis; TSGP4; Mast cell; Basophil
• ISSN: 0965-1748; 1879-0240
• DOI: 10.1016/j.ibmb.2008.06.002

Inflammation is an important vertebrate defense mechanism against ecto-parasites for which ticks have evolved numerous mechanisms of modulation. AM-33 and TSGP4, related lipocalins from the soft ticks Argas monolakensis and Ornithodoros savignyi bind cysteinyl leukotrienes with high affinity as measured by isothermal titration calorimetry. This was confirmed in a smooth muscle bioassay that measured contraction of guinea pig ileum induced by leukotriene C 4 where both proteins inhibited contraction effectively. Conservation of this function in two diverse soft tick genera suggests that scavenging of cysteinyl leukotrienes evolved in the ancestral soft tick lineage. In addition soft ticks also evolved mechanisms that target other mediators of inflammation that include scavenging of histamine, serotonin, leukotriene B 4, thromboxane A 2, ATP and inhibition of the complement cascade. Inhibitors of blood-coagulation and platelet aggregation were also present in the ancestral soft tick lineage. Because histamine and cysteinyl leukotrienes are mainly produced by mast cells and basophils, and these cells are important in the mediation of tick rejection reactions, these findings indicate an ancient antagonistic relationship between ticks and the immune system. As such, modulation of the hemostatic system as well as inflammation was important adaptive responses in the evolution of a blood-feeding lifestyle in soft ticks.