Diversity in motile responses of human neutrophil granulocytes: functional meaning and cytoskeletal basis.

Different agonists induce motility and shape changes, but only a specific polarized shape is correlated with directed migration. An intact and dynamic actin network appears to be important for motility and migration. Motility is usually associated with an increased level of F-actin, and a specific location of F-actin into surface protrusions. For locomotion, a specific location of F-actin, rather than a large net increase in F-actin appears to be of importance. Three major groups of responses can be distinguished on the basis of the type of shape changes, functional activity and organization of F-actin. 1. Agents capable of polarizing cells, such as chemotactic peptides, and microtubule-disassembling agents elicit, at appropriate concentrations, a marked chemokinetic response, but little if any fluid pinocytosis. F-actin shows a polar location, being concentrated mainly in the protrusions at the leading front. Chemotactic peptide also induces an increase in the level of F-actin and cytoskeleton-associated actin. It is, however, not clear if front-tail polarity and locomotion, induced by chemotactic peptide after longer time of stimulation, correlate with an actual increase in the level of cytoskeleton-associated actin. 2. Activators of protein kinase C such as PMA and diacylglycerols, induce nonpolar cells with surface projections. PMA and diacylglycerols stimulate pinocytosis substantially. All three agents tend to inhibit locomotion or chemotaxis as an immediate response. They also increase the percentage of cytoskeletal actin, and induce an enrichment of F-actin in surface projections. 3. Circus movement may occur in response to D20. These cells show little or no stimulation of locomotion or pinocytosis. Thus the functional significance of this motor response remains to be elucidated. We conclude that different agonists can induce motility and shape changes, but not necessarily chemotaxis. Only a polarized shape is correlated with directed locomotion. An intact and dynamic actin network appears to be important for motility including locomotion. Motility is usually associated with an increased level of F-actin, and a specific location of F-actin into surface protrusions. The actin-associated proteins alpha-Actinin, myosin and actin-binding protein appear also to be important for pseudopod formation. For locomotion, a specific location of F-actin, rather than a large net increase in F-actin may be of importance.