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Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity.

Nature communications (2018-01-06)
Oliver Werz, Jana Gerstmeier, Stephania Libreros, Xavier De la Rosa, Markus Werner, Paul C Norris, Nan Chiang, Charles N Serhan
ABSTRACT

Proinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1. E. coli activates M2 macrophages to translocate 5-LOX and 15-LOX-1 to different subcellular locales in a Ca2+-dependent manner. Neither attenuated nor non-pathogenic E. coli mobilize Ca2+ or activate LOXs, rather these bacteria stimulate prostaglandin production. RvD5 is more potent than leukotriene B4 at enhancing macrophage phagocytosis. These results indicate that M1 and M2 macrophages respond to pathogenic bacteria differently, producing either leukotrienes or resolvins that further distinguish inflammatory or pro-resolving phenotypes.

MATERIALS
Product Number
Brand
Product Description

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Histopaque®-1077, sterile-filtered, density: 1.077 g/mL
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Duolink® In Situ PLA® Probe Anti-Rabbit PLUS, Affinity purified Donkey anti-Rabbit IgG (H+L)
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Duolink® In Situ PLA® Probe Anti-Mouse MINUS, Affinity purified Donkey anti-Mouse IgG (H+L)
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Duolink® In Situ Detection Reagents FarRed
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Anti-ALOX5 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution

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