Characterization of leukotriene B3: comparison of its biological activities with leukotriene B4 and leukotriene B5 in complement receptor enhancement, lysozyme release and chemotaxis of human neutrophils

1. Leukotriene (LT) B3 was prepared by total chemical synthesis and its identity was confirmed by nuclear magnetic resonance analysis and proton homonuclear plot of connectivities and chemical shift assignments. The effects of LTB3 on Complement Receptor enhancement, chemotaxis and lysozyme release in human neutrophils (PMN) were compared with those of LTB4 and LTB5. 2. LTB3 and LTB4 elicited a virtually identical dose- and time-dependent enhancement in complement receptors type 1 (CR1) and type 3 (CR3) and release of lysozyme. LTB5 was approximately 100 times less potent than LTB4 in enhancing CR1 and CR3, whereas it was 10,000 times less potent than LTB4 in releasing lysozyme from human PMN. 3. LTB3 and LTB5 were respectively 5- and 100-fold less potent than LTB4 in eliciting chemotaxis. 4. These findings indicate that the pro-inflammatory potential of LTB3 and LTB4 are similar, whereas LTB5 is substantially less potent as an inflammatory mediator. 5. The finding that LTB5 is a weak and partial agonist relative to LTB3 and LTB4 could be due to the rigidity of the C-17-C-18 double bond in LTB5. This may interfere with the active site specificity of LTB5 to a substantial extent. 6. One approach to the development of antagonists to the LTB4 receptor may be to establish a rigid structure in the C-17-C-18 region of the LTB4 molecule.