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Lipoxin A 4 and lipoxin B 4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion
Author(s) -
Nigam Santosh,
Fiore Stefano,
Luscinskas Francis W.,
Serhan Charles N.
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041430316
Subject(s) - lipoxin , arachidonic acid , chemistry , phospholipid , phosphatidic acid , biochemistry , lipoxygenase , lipid signaling , receptor , enzyme , membrane
Abstract The profiles of actions of lipoxin A 4 (LXA 4 ) and lipoxin B 4 (LXB 4 ), two lipoxygenase‐derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA 4 and LXB 4 each stimulated the release of [1‐ 14 C]arachidonic acid from esterified sources in neutrophils. Lipoxin‐induced release of [1‐ 14 C]arachidonic acid was both dose‐ and time‐dependent and was comparable to that induced by the chemotactic peptide f‐met‐leu‐phe. Time‐course studies revealed that lipoxin A 4 and lipoxin B 4 each induced a biphasic release of [1‐ 14 C]arachidonic acid, which was evident within seconds (5–15 sec) in its initial phase and minutes (>30 sec) in the second phase. In contrast, the all‐trans isomers of LXA 4 and LXB 4 did not provoke [1‐ 14 C]AA release. Lipoxin‐induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its β‐oligomers, suggesting the involvement of guaninine nucleotide‐binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with [1‐ 14 C]arachidonic acid and [ 3 H]palmitic acid showed that phosphatidylcholine was a major source of lipoxin‐induced release of [1‐ 14 C]arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA 4 and LXB 4 (10 −8 ‐10 −6 M) stimulated the release of [1‐ 14 C]arachidonic acid, neither compound evoked its oxygenation by either the 5‐or 15‐lipoxygenase pathways (including the formation of LTB 4 , 20‐COOH‐LTB 4 , 5‐HETE, or 15‐HETE). LXA 4 and LXB 4 (10 −7 M) each stimulated the elevation of cytosolic Ca 2+ as monitored with Fura 2‐loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of [ 3 H]LTB 4 to its receptor on neutrophils. In addition, they did not stimulate aggregation or induce adhesion of neutrophils to human endothelial cells. Results indicate that both LXA 4 and LXB 4 stimulate the rapid remodeling of neutrophil phospholipids to release arachidonic acid without provoking either aggregation or the formation of lipoxygenase‐derived products within a similar temporal and dose range. Together they indicate that LXA 4 and LXB 4 display selective actions with human neutrophils and suggest that these eicosanoids possess unique profiles of action which may regulate neutrophil function during inflammation.