TY - JOUR
T1 - New maresin conjugates in tissue regeneration pathway counters leukotriene D4–stimulated vascular responses
AU - Chiang, Nan
AU - Riley, Ian R.
AU - Dalli, Jesmond
AU - Rodriguez, Ana R.
AU - Spur, Bernd W.
AU - Serhan, Charles N.
N1 - Publisher Copyright:
© FASEB.
PY - 2018/7
Y1 - 2018/7
N2 - Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proinflammatory 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 D4 (LTD4; 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, LTD4 (1–100 nM) induced negative inotropic action and lowered heartbeats 20–30%. Each MCTR (1–100 nM) prevented LTD4-reduced heart rates. With human cysteinyl leukotriene receptor-1 (CysLT1) expressed in CHO cells, each MCTR (10–100 nM) significantly reduced LTD4-initiated signaling. To assess the contribution of CysLT1 in the proresolving actions of MCTR, we carried out human macrophage (MF) phagocytosis. Each MCTR (0.1–10 nM) stimulated human MF phagocytosis of live Escherichia coli, whereas LTD4 did not stimulate phagocytosis. MCTR-activated phagocytosis was significantly blocked by a pharmacologic receptor antagonist (MK571). With both CHO-CysLT1 and human MFs, each MCTR competed for specific [3H]-LTD4 binding with apparent lower affinity than LTD4. Thus, each MCTR functionally interacts with human CysLT1 to pharmacologically counter-regulate vascular responses and stimulate physiologic phagocytosis with MFs.—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
AB - Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proinflammatory 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 D4 (LTD4; 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, LTD4 (1–100 nM) induced negative inotropic action and lowered heartbeats 20–30%. Each MCTR (1–100 nM) prevented LTD4-reduced heart rates. With human cysteinyl leukotriene receptor-1 (CysLT1) expressed in CHO cells, each MCTR (10–100 nM) significantly reduced LTD4-initiated signaling. To assess the contribution of CysLT1 in the proresolving actions of MCTR, we carried out human macrophage (MF) phagocytosis. Each MCTR (0.1–10 nM) stimulated human MF phagocytosis of live Escherichia coli, whereas LTD4 did not stimulate phagocytosis. MCTR-activated phagocytosis was significantly blocked by a pharmacologic receptor antagonist (MK571). With both CHO-CysLT1 and human MFs, each MCTR competed for specific [3H]-LTD4 binding with apparent lower affinity than LTD4. Thus, each MCTR functionally interacts with human CysLT1 to pharmacologically counter-regulate vascular responses and stimulate physiologic phagocytosis with MFs.—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
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UR - http://www.scopus.com/inward/citedby.url?scp=85049258993&partnerID=8YFLogxK
U2 - 10.1096/fj.201701493R
DO - 10.1096/fj.201701493R
M3 - Article
C2 - 29490167
AN - SCOPUS:85049258993
SN - 0892-6638
VL - 32
SP - 4043
EP - 4052
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -