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REGIONAL ANESTHESIA AND PAIN MEDICINE

Local Anesthetics Attenuate Lysophosphatidic Acid-Induced Priming in Human Neutrophils

Lars G. Fischer, MD^§, Maria Bremer, Elizabeth J. Coleman, MS, Beate Conrad, Boris Krumm, Ariane Gross^||, Markus W. Hollmann, MD^||, Gerald Mandell, MD, and Marcel E. Durieux, MD, PhD^*

*Department of Anesthesiology, University Hospital Maastricht, The Netherlands, the Departments of Medicine (Infectious Diseases) and Anesthesiology, University of Virginia Health System, Charlottesville, Virginia, §Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische-Wilhelms-Universität, Münster, Germany, ||Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany

Address correspondence and reprint requests to Marcel E. Durieux, MD, PhD, Department of Anesthesiology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Address e-mail to durieux{at}virginia.edu

Lysophosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory responses. We therefore studied its actions on neutrophil (PMN) motility and respiratory burst. Because local anesthetics (LA) inhibit LPA signaling and attenuate PMN responses, we also investigated the effects of LA on these actions. 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 using a cytochrome-c assay of superoxide anion (O₂^-) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10^-6–10^-4 M) for 10 min or 1 h to assess interference with LPA signaling. LPA demonstrated chemoattractive effects towards human PMNs; this effect was concentration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant concentrations decreased O₂^- production induced by LPA/N-formylmethionine-leucyl-phenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, attenuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics.

Implications: Lysophosphatidic acid (LPA) influences two functions of human neutrophils, migration and metabolic activity. It acted as a chemoattractant and a priming–but not activating–agent. Responses to LPA were attenuated by local anesthetics in clinically relevant concentrations.

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