Phospholipase A sub(2) pathway association with macrophage-mediated polycarbonate-urethane biodegradation

Activation of the phospholipase A sub(2) (PLA sub(2)) pathway is a key cell signaling event in the inflammatory response. The PLA sub(2) family consists of a group of enzymes that hydrolyze membrane phospholipids, resulting in the liberation of arachidonic acid (AA), a precursor to pro-inflammatory molecules. Given the well-documented activating role of biomaterials in the inflammatory response to medical implants, the present study investigated the link between PLA sub(2) and polycarbonate-based polyurethane (PCNU) biodegradation, and the effect that material surface had on PLA sub(2) activation in the U937 cell line. PCNUs were synthesized with poly(1, 6-hexyl 1, 2-ethyl carbonate)diol, 1, 4- butanediol and one of two diisocyanates (hexane 1, 6-diisocyanate or 4, 4'- methylene bisphenyl diisocyanate) in varying stoichiometries and incubated with adherent U937 cells. PLA sub(2) inhibiting agents resulted in significantly decreased PCNU biodegradation (, p