Lipoxin A4 and lipoxin B4 stimulate the release but not the oxygenation of arachidonic acid in human neutrophils: Dissociation between lipid remodeling and adhesion

Journal Article · Fri Jun 01 00:00:00 EDT 1990 · Journal of Cellular Physiology; (USA)

DOI:https://doi.org/10.1002/jcp.1041430316· OSTI ID:6643918

Nigam, S; Fiore, S; Luscinskas, F W; Serhan, C N ^[1]

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1. Brigham and Women's Hospital, Boston, MA (USA)

The profiles of actions of lipoxin A4 (LXA4) and lipoxin B4 (LXB4), two lipoxygenase-derived eicosanoids, were examined with human neutrophils. At nanomolar concentrations, LXA4 and LXB4 each stimulated the release of (1-14C)arachidonic acid from esterified sources in neutrophils. Lipoxin-induced release of (1-14C)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 A4 and lipoxin B4 each induced a biphasic release of (1-14C)arachidonic acid, which was evident within seconds (5-15 sec) in its initial phase and minutes (greater than 30 sec) in the second phase. In contrast, the all-trans isomers of LXA4 and LXB4 did not provoke (1-14C)AA release. Lipoxin-induced release of arachidonic acid was inhibited by prior treatment of the cells with pertussis toxin but not by its beta-oligomers, suggesting the involvement of guaninine nucleotide-binding regulatory proteins in this event. Dual radiolabeling of neutrophil phospholipid classes with (1-14C)arachidonic acid and (3H)palmitic acid showed that phosphatidylcholine was a major source of lipoxin-induced release of (1-14C)arachidonic acid. They also demonstrated that lipoxins rapidly stimulate both formation of phosphatidic acid as well as phospholipid remodeling. Although both LXA4 and LXB4 (10(-8)-10(-6) M) stimulated the release of (1-14C)arachidonic acid, neither compound evoked its oxygenation by either the 5- or 15-lipoxygenase pathways (including the formation of LTB4, 20-COOH-LTB4, 5-HETE, or 15-HETE). LXA4 and LXB4 (10(-7) M) each stimulated the elevation of cytosolic Ca2+ as monitored with Fura 2-loaded cells, albeit to a lesser extent than equimolar concentrations of FMLP. Neither lipoxin altered the binding of (3H)LTB4 to its receptor on neutrophils.

• OSTI ID: 6643918
• Journal Information: Journal of Cellular Physiology; (USA), Vol. 143:3; ISSN 0021-9541
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
SECRETION
EICOSANOIC ACID
BIOCHEMICAL REACTION KINETICS
ADHESION
BIOLOGICAL PATHWAYS
CALCIUM COMPOUNDS
CARBON 14 COMPOUNDS
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
DOUBLE LABELLING
ENDOTHELIUM
LIPIDS
MAN
NEUTROPHILS
PHOSPHOLIPIDS
RECEPTORS
TIME DEPENDENCE
TOXINS
TRACER TECHNIQUES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL TISSUES
ANIMALS
ANTIGENS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
ESTERS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LABELLING
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PRIMATES
PROTEINS
REACTION KINETICS
TISSUES
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques