Effect of lysophosphatidic acid on motility, polarisation and metabolic burst of human neutrophils

The effect of lysophosphatidic acid (LPA) on human neutrophil activation was examined by a combination of automated tracking assays, cell shape measurements and assays of the metabolic burst by means of 7-dimethylamino-naphthalene-1, 2-dicarbonic acid hydrazide (DNDH)-dependent chemiluminescence. LPA powerfully stimulated polarisation and motility. Polarisation became detectable at 2 µM LPA and virtually 100% of cells were polarised at 20 µM LPA. Cell motility increased with the degree of polarisation, and was diminished at high LPA concentration, but this decrease was reversed by albumin. LPA also inhibited the metabolic burst response to both n-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). Inhibition of the PMA-induced metabolic burst by LPA was not affected by pertussis toxin, showing that the effect was not mediated by the pertussis toxin-sensitive heterotrimeric G protein, and that inhibition of the PMA-stimulated metabolic burst by LPA could result from a direct action of LPA on the small cytosolic GTP-binding proteins. These results indicate that lysophosphatidic acid production by thrombin-activated platelets could play a significant role in the regulation of the inflammatory response.