Calcium ionophore synergizes with bacterial lipopolysaccharides in activating macrophage arachidonic acid metabolism

LPS, a major component of Gram-negative bacterial cell walls, prime macrophages for greatly enhanced arachidonic acid [20:4] metabolism when the cells are subsequently stimulated. The LPS-primed macrophage has been used as a model system in which to study the role of Ca2+ in the regulation of 20:4 m...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 1988-02, Vol.167 (2), p.623-631
Main Authors: ADEREM, A. A, COHN, Z. A
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acid
Arachidonic Acids - metabolism
Biological and medical sciences
Calcimycin - pharmacology
Calcium - pharmacology
Drug Synergism
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Immunobiology
Lipopolysaccharides - pharmacology
Lipoxygenase - metabolism
Macrophage Activation - drug effects
Macrophages - metabolism
Mice
Mice, Inbred ICR
Myeloid cells: ontogeny, maturation, markers, receptors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:LPS, a major component of Gram-negative bacterial cell walls, prime macrophages for greatly enhanced arachidonic acid [20:4] metabolism when the cells are subsequently stimulated. The LPS-primed macrophage has been used as a model system in which to study the role of Ca2+ in the regulation of 20:4 metabolism. The Ca2+ ionophore A23187 (0.1 microM) triggered the rapid release of 20:4 metabolites from LPS-primed macrophages but not from cells not previously exposed to LPS. Macrophages required exposure to LPS for at least 40 min before A23187 became effective as a trigger. A23187 (0.1 microM) also synergized with PMA in activating macrophage 20:4 metabolism. The PMA effect could be distinguished from that of LPS since no preincubation with PMA was required. A23187 greatly increased the amount of lipoxygenase products secreted from LPS-primed macrophages, leukotriene C4 synthesis being increased 150-fold. LPS-primed macrophages, partially permeabilized to Ca2+ with A23187, were used to titrate the Ca2+ concentration dependence of the cyclooxygenase and lipoxygenase pathways. Cyclooxygenase metabolites were detected at an order of magnitude lower Ca2+ concentration than were lipoxygenase products. The data suggest that Ca2+ regulates macrophage 20:4 metabolism at two distinct steps: an increase in intracellular Ca2+ regulates the triggering signal and relatively higher Ca2+ concentrations are required for 5-lipoxygenase activity.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.167.2.623