Human Monocytes Respond to Leukotriene B4 with a Transient Increase in Cytosolic Calcium

To define the intracellular activation events stimulated by leukotriene B4 (LTB4) in human monocytes, we investigated the transient increase in cytosolic free calcium levels ([Ca2+]i) elicited by this lipid mediator. Using clutriated human monocytes, LTB4 caused a dose-dependent increase in [Ca21]i with an ED50 of 1.0 nM. The LTB4-induced [Ca21]i response exhibited ligand selectivity, with both the diastereomer 5S-12S-dillETE and the 20-COOH LTB4 inactive at 500 nM, while 20-OH LTB4 was a partial agonist with an approximate ED50 of 10 nM. This response demonstrated stimulus-specific deactivation and was inhibited by the specific LTB4 receptor antagonist LY-223982. These results suggest that LTB4 stimulated an increase in [CA2+]i via interaction with a defined LTB4 receptor. The inhibitory effects of pertusis toxin and PMA on the LTB4-induced [Ca2+]i suggest that a receptor-linked guanine nucleotide-binding protein and protein kinase C are involved in the regulation of the LTB4-elicited increase in [Ca2+]i. This LTB4-induced cell activation event may play a key role in the functional responses elicited by LTB4 in human monocytes.