Annexin A1 mediates the anti-inflammatory effects during the granulocytic differentiation process in all-trans retinoic acid-treated acute promyelocytic leukemic cells (63.2)

Abstract

Annexin A1 (AnxA1) originating from neutrophils and their microparticles (MPs) plays an important anti-inflammatory role. The role of AnxA1 during the process of granulocytic differentiation is still unknown. All-trans retinoic acid (ATRA) can induce differentiation of acute promyelocytic leukemic(APL) cells into mature granulocytes. We investigated whether or not AnxA1 contributed to the anti-inflammatory properties of ATRA-treated APL (NB4; ATRA-NB) cells. We found that ATRA was able to enhance the surface expression of AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1-containing MPs from ATRA-NB4 cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA-NB4 cells in their transmigratory and adhesive activity. In addition, the transmigratory activity of ATRA-NB4 cells can be significantly enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that endogenous AnxA1 may contribute to the anti-migratory effects. Finally, ATRA-NB4-derived MPs could also inhibit recipient cells in their transmigratory and adhesive activities and these anti-inflammatory effects could be inhibited by pretreatment of MPs with an anti-AnxA1 antibody. Further studies demonstrated that FITC-labeled AnxA1 could be transport from MPs to the membrane of recipient ATRA-NB4 cells. We conclude that biologically active AnxA1 may play a role in the anti-inflammatory properties of ATRA-APL cells during the process of granulocytic differentiation.