Local anesthetics attenuate lysophosphatidic acid-induced priming in humanneutrophils

Lysoyhosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory respon ses. We therefore studied its actions on neutrophil (PMN) motility and resp iratory burst. Because local anesthetics (LA) inhibit LPA signaling and att enuate PMN responses, we also investigated the effects of LA on these actio ns. Chemotaxis of human PMNs under agarose toward LPA (10(-10)-10(-3)M) was studied, with and without 1 h prior incubation in lidocaine (10(-9)-10(-4) M). Priming as well as activating effects of LPA on PMNs were measured usi ng a cytochrome-e assay of superoxide anion (O-2(-)) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10(-6)-1 0(-4) M) for 10 min or 1 h to assess interference with LPA signaling. LPA d emonstrated chemoattractive effects towards human PMNs; this effect was con centration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant conce ntrations decreased O-2(-) production induced by LPA/N-formylmethionine-leu cylphenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, atte nuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics.