Inside platelet-leukocyte cross-talk in aspirin exacerbated respiratory disease. (A) In AERD, enhanced propensity of platelets to adhere to leukocytes translates into increased biosynthesis and release of LTC₄ that is metabolized to LTE₄ by the activity of enzymes present in plasma. LTE₄ may interact with platelet P2Y12 receptor, thus inducing platelet P-selectin expression and facilitating the formation of platelet-leukocyte aggregates. Other platelet products, such as GM-CSF, can be released and may activate leukocyte 5-LO and induce a pro-adhesion phenotype and prolong the survival of eosinophils. As shown in panel B (from Figure 1 in the article by Laidlaw et al beginning on page 3790¹ ), nasal polyps from subjects with AERD contained many extravascular platelets that co-localized with leukocytes. In this scenario, NSAID treatment may increase the biosynthesis of cys-LTs. NSAIDs inhibit platelet COX-1 that can cause the accumulation and release of free AA that can be taken up by leukocytes thus inducing 5-LO translocation and enhancing cys-LT generation. PGH₂ indicates prostaglandin-H₂; and TXS, thromboxane synthase.