Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites

• Published in: The Journal of experimental medicine Vol. 164; no. 1; pp. 165 - 179
• Main Authors: ADEREM, A. A, COHEN, D. S, WRIGHT, S. D, COHN, Z. A
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.07.1986; The Rockefeller University Press
• Subjects: Animals; Arachidonic Acid; Arachidonic Acids - metabolism; Biological and medical sciences; Dose-Response Relationship, Immunologic; Female; Fundamental and applied biological sciences. Psychology; Inflammation; Latex; Lipopolysaccharides - pharmacology; Macrophage Activation; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred ICR; Microspheres; Molecular and cellular biology; Receptors, Complement - physiology; Receptors, Complement 3b; T-Lymphocytes - immunology; Time Factors; Vertebrata; Mammalia; Mouse; Metabolite; Secretion; Rodentia; Lipopolysaccharide; Bacteria; Stimulation; Inflammation; Arachidonic acid; Macrophage
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.164.1.165

Preincubation of resident peritoneal macrophages with 10-100 ng/ml LPS for 60 min resulted in the cells becoming primed for enhanced (three-to eightfold higher) arachidonic acid (20:4) secretion in response to a variety of triggers. The half-maximal concentration of LPS required for priming was 10 ng/ml irrespective of whether the trigger was particulate (examples: zymosan or immune complexes) or soluble (such as PMA or A23187). Similarly, the time required for half-maximal priming of macrophages was 20 min irrespective of which trigger was used. The primed state persisted for at least 30 h. LPS-priming of macrophages also affected the kinetics of 20:4 metabolite secretion. The lag phase characteristically observed when 20:4 secretion is triggered was reduced in LPS-primed cells. Furthermore, LPS-primed cells secreted 20:4 metabolites when challenged with latex beads, while unprimed cells did not. These data suggest that stimuli such as zymosan, which elicit 20:4 secretion in macrophages, promote two signals, a priming signal and a triggering signal. LPS is capable of establishing the priming signal but not the triggering signal, while latex promotes the triggering signal but is unable to prime the cells for 20:4 release. LPS did not effect the profile of 20:4 metabolites secreted in response to any of the triggers, nor did it effect the profile of products synthesized from exogenously added 20:4, suggesting that it did not regulate the 20:4 cascade at the level of either the cyclooxygenase or lipoxygenase pathways. Macrophages respond to LPS without the intervention of T lymphocytes, since the macrophages from nude mice could be primed for enhanced 20:4 secretion.