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New maresin conjugates in tissue regeneration pathway counters leukotriene D 4 –stimulated vascular responses
Author(s) -
Chiang Nan,
Riley Ian R.,
Dalli Jesmond,
Rodriguez Ana R.,
Spur Bernd W.,
Serhan Charles N.
Publication year - 2018
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/fj.201701493r
Subject(s) - phagocytosis , leukotriene d4 , leukotriene , lipid signaling , microbiology and biotechnology , chemistry , inflammation , receptor , proinflammatory cytokine , lucifer yellow , biology , pharmacology , immunology , antagonist , biochemistry , gap junction , asthma , intracellular
Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proin flammatory eicosanoids to specialized proresolving mediators, including a recently identified new pathway of mediators, termed maresin conjugates in tissue regeneration (MCTR), which includes MCTR1, MCTR2, and MCTR3. Here, we addressed whether each MCTR can impact the known vascular actions of cysteinyl leukotrienes. Leukotriene D 4 (LTD 4 ; 1.5 nmol/mouse) initiated vascular leakage in mouse cremaster vessels, which was reduced (>75%) by MCTR1 and MCTR2 (0.15 nmol each). With isolated Ciona intestinalis (sea squirt) primordial hearts, LTD 4 (1–100 nM) induced negative inotropic action and lowered heartbeats 20–30%. Each MCTR (1–100 nM) prevented LTD 4 ‐reduced heart rates. With human cysteinyl leukotriene receptor‐1 (CysLT1) expressed in CHO cells, each MCTR (10–100 nM) significantly reduced LTD 4 ‐initiated signaling. To assess the contribution of CysLT1 in the proresolving actions of MCTR, we carried out human macrophage (MΦ) phagocytosis. Each MCTR (0.1–10 nM) stimulated human MΦ phagocytosis of live Escherichia coli , whereas LTD 4 did not stimulate phagocytosis. MCTR‐activated phagocytosis was significantly blocked by a pharmacologic receptor antagonist (MK571). With both CHO‐CysLT1 and human MΦs, each MCTR competed for specific [ 3 H]‐LTD 4 binding with apparent lower affinity than LTD 4 . Thus, each MCTR functionally interacts with human CysLT1 to pharmacologically counter‐regulate vascular responses and stimulate physiologic phagocytosis with MΦs.—Chiang, N., Riley, I. R., Dalli, J., Rodriguez, A. R., Spur, B. W., Serhan, C. N. New maresin conjugates in tissue regeneration pathway counters leukotriene D4‐ stimulated vascular responses. FASEB J. 32, 4043–4052 (2018). www.fasebj.org