Do phosphoinositide 3-kinases direct lymphocyte navigation?

Phosphoinositide 3-kinase (PI3K)-dependent signalling pathways have been suggested to have pivotal roles in determining the polarity of leukocytes moving toward a chemotactic gradient, a process termed chemotaxis. Current perceptions concerning the role of PI3K in leukocyte migration are based predominantly around evidence derived from single-cell organisms and analysis of neutrophil migration from mice deficient in the gamma-isoform of the p110 catalytic subunit. With regard to directed T-lymphocyte migration, there is convincing evidence for the activation of PI3K isoforms in T lymphocytes by several chemokines. However, there is a growing body of evidence, which now indicates that in T lymphocytes at least, PI3K activation can be a dispensable signal for directed cell migration in certain settings. In fact, evidence is emerging that during directed cell migration, T lymphocytes use biochemical pathways distinct from those adopted by monocytes. The non-universal role of PI3K in directional cell migration and the existence of cell-specific signalling pathways for chemotactic responses has important implications for the validation of effective new targets for inflammation, where one aim is to block migration of leukocytes to the site of inflammatory lesion.