Human Monocytes Respond to Leukotriene B 4 with a Transient Increase in Cytosolic Calcium

Abstract

To define the intracellular activation events stimulated by leukotriene B 4 (LTB 4) in human monocytes, we investigated the transient increase in cytosolic free calcium levels ([Ca 2+] i) elicited by this lipid mediator. Using clutriated human monocytes, LTB 4 caused a dose-dependent increase in [Ca 21] i with an ED 50 of 1.0 n M. The LTB 4-induced [Ca 21] i response exhibited ligand selectivity, with both the diastereomer 5S-12S-dillETE and the 20-COOH LTB 4 inactive at 500 n M, while 20-OH LTB 4 was a partial agonist with an approximate ED 50 of 10 n M. This response demonstrated stimulus-specific deactivation and was inhibited by the specific LTB 4 receptor antagonist LY-223982. These results suggest that LTB 4 stimulated an increase in [CA 2+] i via interaction with a defined LTB 4 receptor. The inhibitory effects of pertusis toxin and PMA on the LTB 4-induced [Ca 2+] i suggest that a receptor-linked guanine nucleotide-binding protein and protein kinase C are involved in the regulation of the LTB 4-elicited increase in [Ca 2+] i. This LTB 4-induced cell activation event may play a key role in the functional responses elicited by LTB 4 in human monocytes.