Normally, cyclooxygenases (COX) carry out stereospecific oxygenation of arachidonic acid to generate prostaglandins. When treated with aspirin (acetylsalicylic acid, ASA), dimeric cyclooxygenase 2 (COX2, PTGS2 dimer) can be acetylated. ASA covalently modifies PTGS2 by acetylating a serine residue at position 530 within the cyclooxygenase active site (Lucido et al. 2016). Acetylated PTGS2 dimer (Ac-PTGS2 dimer) changes the oxygenation stereospecificity towards its substrates, perhaps by steric shielding effects (Tosco 2013), producing a shift in lipid mediator production. Ac-PTGS2 dimer expressed in neutrophils can be acetylated by ASA, which now switches to mediate biosynthesis of precursors of endogenous antiinflammatory mediators. Ac-PTGS2 dimer is able to incorporate molecular oxygen into eicosapentaenoic acid (EPA) to form the stereoisomers 18(S)- and 18(R)-hydroperoxy-eicosapentaenoic acid (18(S)- and 18(R)-HpEPE respectively) (Serhan et al. 2000, Oh et al. 2011).