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Pro‐Resolving Mediator Production by Human Phagocytes and their Transcellular Biosynthesis with Microparticles in Inflammation‐Resolution
Author(s) -
Dalli Jesmond,
Serhan Charles
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1168.4
Subject(s) - efferocytosis , lipid signaling , zymosan , inflammation , phagocyte , chemistry , microbiology and biotechnology , phagocytosis , mediator , apoptosis , macrophage , immunology , biology , biochemistry , in vitro
Phagocytes are central in orchestrating the acute host response during inflammation and its timely resolution. Using lipid mediator (LM) metabololipidomcs, we assessed LM levels in neutrophils (PMN), apoptotic PMN and macrophages. During efferocytosis, macrophages upregulate the biosynthesis of specialized pro‐resolving mediators (SPM), including resolvin (Rv) D1 and RvD2, that were further elevated by PMN microparticles (MP). Using deuterium labeled precursors we found that both apoptotic PMN and MP donated precursors to macrophages that were utilized for transcellular SPM biosynthesis. Fresh PMN from peripheral blood with zymosan gave predominantly leukotriene B4, whereas apoptotic PMN displayed both elevated prostaglandin E2 and lipoxin (LX) B4. Lineage differentiated macrophages showed distinct LM profiles where M2 macrophages gave higher SPM including maresin 1 and lower prostaglandins then M1. These profiles were regulated during efferocytosis where M1 cells gave increased SPM including LXA4 while overall LM biosynthesis was reduced in M2. Together these findings establish the LM signatures of human phagocytes and their regulation during distinct stages of acute inflammation‐resolution. This work was supported by the NIH (grants GM038765 and GM095467).