TY - JOUR
T1 - Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils
AU - Bando, Tomoyuki
AU - Fujita, Setsuko
AU - Nagano, Naoko
AU - Yoshikawa, Soichiro
AU - Yamanishi, Yoshinori
AU - Minami, Masashi
AU - Karasuyama, Hajime
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Basophils have been erroneously considered as minor relatives of mast cells, due to some phenotypic similarity between them. While recent studies have revealed non-redundant roles for basophils in various immune responses, basophil-derived effector molecules, including lipid mediators, remain poorly characterized, compared to mast cell-derived ones. Here we analyzed and compared eicosanoids produced by mouse basophils and mast cells when stimulated with IgE plus allergens. The production of 5-LOX metabolites such as LTB4 and 5-HETE was detected as early as 0.5 h post-stimulation in both cell types, even though their amounts were much smaller in basophils than in mast cells. In contrast, basophils and mast cells showed distinct time course in the production of COX metabolites, including PGD2, PGE2 and 11-HETE. Their production by mast cells was detected at both 0.5 and 6 h post-stimulation while that by basophils was detectable only at 6 h. Of note, mast cells showed 8–9 times higher levels of COX-1 than did basophils at the resting status. In contrast to unaltered COX-1 expression with or without stimulation, COX-2 expression was up-regulated in both cell types upon activation. Importantly, when activated, basophils expressed 4–5 times higher levels of COX-2 than did mast cells. In accordance with these findings, the late-phase production of the COX metabolites by basophils was completely ablated by COX-2 inhibitor whereas the early-phase production by mast cells was blocked by COX-1 but not COX-2 inhibitor. Thus, the production of COX metabolites is differentially regulated by COX-1 and COX-2 in basophils and mast cells.
AB - Basophils have been erroneously considered as minor relatives of mast cells, due to some phenotypic similarity between them. While recent studies have revealed non-redundant roles for basophils in various immune responses, basophil-derived effector molecules, including lipid mediators, remain poorly characterized, compared to mast cell-derived ones. Here we analyzed and compared eicosanoids produced by mouse basophils and mast cells when stimulated with IgE plus allergens. The production of 5-LOX metabolites such as LTB4 and 5-HETE was detected as early as 0.5 h post-stimulation in both cell types, even though their amounts were much smaller in basophils than in mast cells. In contrast, basophils and mast cells showed distinct time course in the production of COX metabolites, including PGD2, PGE2 and 11-HETE. Their production by mast cells was detected at both 0.5 and 6 h post-stimulation while that by basophils was detectable only at 6 h. Of note, mast cells showed 8–9 times higher levels of COX-1 than did basophils at the resting status. In contrast to unaltered COX-1 expression with or without stimulation, COX-2 expression was up-regulated in both cell types upon activation. Importantly, when activated, basophils expressed 4–5 times higher levels of COX-2 than did mast cells. In accordance with these findings, the late-phase production of the COX metabolites by basophils was completely ablated by COX-2 inhibitor whereas the early-phase production by mast cells was blocked by COX-1 but not COX-2 inhibitor. Thus, the production of COX metabolites is differentially regulated by COX-1 and COX-2 in basophils and mast cells.
KW - Basophils
KW - COX-2
KW - Eicosanoids
KW - LC-MS/MS
KW - Mast cells
KW - Prostaglandins
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U2 - 10.1016/j.bbrep.2017.03.004
DO - 10.1016/j.bbrep.2017.03.004
M3 - Article
AN - SCOPUS:85015149850
VL - 10
SP - 82
EP - 87
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
SN - 2405-5808
ER -