FIG. 3.

Schematic diagram of the most probable 3OC12-HSL signaling pathway. Because inhibition of tyrosine kinases (by Gefinitib), of phospholipase C (PLC) (by U73122), of protein kinase C (PKC) (by Staurosporin), and of mitogen-activated protein kinase (MEK) (by SB203580) inhibited the chemotaxis induced by 3OC12-HSL, we propose that the putative 3OC12-HSL receptor binds to a tyrosine kinase and induces the signaling pathway indicated on the left. This pathway differs from that for IL-8 because the IL-8 receptor is associated with G protein (the signal can be inhibited by pertussis toxin) (signaling pathway shown on the right). Triggering of the IL-8 receptor also leads to activation of phospholipase C and phosphatidylinositol-3-kinase (PI3K). The latter presumably activates mitogen-activated protein kinase and thus could represent an alternative or additional signaling pathway for IL-8, and this explains why preincubation of PMN with 3OC12-HSL reduced the chemotaxis toward IL-8 and not vice versa. On the right, the well-established signaling pathway for the IL-8-receptor (IL-8-R) is shown; activation of adenylate cyclase (AC) leads to upregulation of cyclic AMP (cAMP) and eventually upregulation of protein kinase A (PKA). DAG, diacylglycerol, Erk, extracellular signal-regulated kinase.