The protein kinase C inhibitor H-7 activates human neutrophils: effect on shape, actin polymerization, fluid pinocytosis and locomotion.
The present study demonstrates new properties of H-7. The protein kinase inhibitor H-7 is a potent activator of several neutrophil functions. Stimulation of initially spherical nonmotile neutrophils elicits vigorous shape changes within a few seconds, increases in cytoskeletal actin, altered F-actin distribution, increased adhesiveness and a relatively small increase in pinocytic activity. H-7 has also chemokinetic activities. Depending on the experimental condition, H-7 may elicit or inhibit neutrophil locomotion. It failed to induce chemotaxis. Thus, the response pattern elicited by H-7 is different from that of other leukocyte activators such as chemotactic peptides, PMA or diacylglycerols. The finding that H-7 can elicit shape changes, actin polymerization and pinocytosis suggests that these events can occur without activation of protein kinase C (PKC). PMA-induced shape changes and stimulation of pinocytosis were not inhibited by H-7.
Institute of Pathology, University of Bern, Switzerland.
H U
HU
Keller
V
V
Niggli
A
A
Zimmermann
R
R
Portmann
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000199:Actins / Q000097:blood*; D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003911:Dextrans / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides; D010873:Pinocytosis / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D000199:Actins; D003911:Dextrans; D005452:Fluoresceins; D007546:Isoquinolines; D009842:Oligopeptides; D010879:Piperazines; C015219:fluorescein isothiocyanate dextran; C021642:F-chemotactic peptide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D016650:Fluorescein-5-isothiocyanate