From inflammation to resolution: eosinophils emerge as a source of Resolvin D1

Eosinophils are widely recognized as pro-inflammatory cells due to their diverse secretory repertoire. Beyond cytokines, they produce bioactive lipid mediators, including arachidonic acid-derived prostanoids and leukotrienes. We hypothesized that eosinophils can also synthesize Resolvin D1 (RvD1), a specialized pro-resolving mediator derived from docosahexaenoic acid. We employed (i) an allergic pleurisy model in C57BL/6, BALB/c, and eosinophil-deficient (ΔdblGATA-/-) mice analyzed at 4, 24, 48, and 72 h; (ii) in vitro differentiated murine eosinophils; and (iii) purified human blood eosinophils from healthy donors. In allergic pleurisy, eosinophils were absent at 4 h, peaked at 24 h, and declined thereafter, remaining elevated through 72 h. Recruitment was accompanied by increased lipid body formation, especially at 24 h (n ≥ 5; p ≤ 0.05), coinciding with elevated LTC4, while RvD1 remained at baseline. At 48 and 72 h, LTC4 declined as RvD1 increased. RvD1 production at 72 h was impaired in ΔdblGATA-/- mice versus wild-type (n = 5; p ≤ 0.05) and positively correlated with pleural eosinophil numbers (r² = 0.8; p < 0.05) in C57BL/6, suggesting an eosinophil-dependent source. In vitro, murine eosinophils rapidly generated RvD1 after stimulation with A23187 (3 μM) or arachidonic acid (10 μM) (1 h; preliminary data). Similarly, purified human eosinophils produced RvD1 in response to A23187 (n = 4; p ≤ 0.05), indicating the enzymatic machinery required for its biosynthesis. We then tested physiological stimuli, including CCL11 (100 ng/mL), PGD2 (25 nM), and selective DP1/DP2 agonists (BW245C, DK-PGD2). RvD1 was induced by CCL11 and DP1 activation, while both CCL11 and PGD2 promoted LTC4 synthesis (n = 4; p ≤ 0.05), highlighting selective regulation of lipid mediator biosynthesis. Collectively, these findings identify eosinophils as a previously unrecognized source of RvD1, supporting a broader role for these cells in the active resolution of inflammation.