Functional characterization of a synthetic abscisic acid analog with anti-inflammatory activity on human granulocytes and monocytes

► Abscisic acid (ABA) is an inflammatory hormone in human granulocytes and monocytes. ► We describe the synthesis and function of an ABA antagonist. ► This analog inhibits ABA binding and action on granulocytes and monocytes in vitro. ► This analog may become a useful tool to abrogate ABA function in animals. The phytohormone abscisic acid (ABA), in addition to regulating several important physiological functions in plants, is also produced and released by human granulocytes and monocytes where it stimulates cell activities involved in the innate immune response. Here we describe the properties of an ABA synthetic analog that competes with the hormone for binding to human granulocyte membranes and to purified recombinant LANCL2 (the human ABA receptor) and inhibits several ABA-triggered inflammatory functions of granulocytes and monocytes in vitro: chemotaxis, phagocytosis, reactive oxygen species production and release of prostaglandin E 2 (PGE 2) by human granulocytes, release of PGE 2 and of monocyte chemoattractant protein-1 by human monocytes. This observation provides a proof of principle that ABA antagonists may represent a new class of anti-inflammatory agents.