Differential role of an atypical protein kinase C, PKC zeta, in regulation of human eosinophil and neutrophil functions.
BACKGROUND
Protein kinase C (PKC) comprises a family of isoenzymes playing a key role in downstream signaling and cell functions. PKCs are grouped according to molecular structure and mode of activation: 'conventional' PKCs (alpha, betaI, betaII, gamma), 'novel' PKCs (delta, epsilon, mu, theta, eta), and 'atypical' PKCs (zeta, tau/lambda). Here we compared the influence of PKC zeta on the function of human eosinophils and neutrophils.


METHODS
After pretreating the cells with a myristoylated specific PKC zeta inhibitor, a myristoylated PKC eta inhibitor, or bisindolylmaleimide I (Bis I; an inhibitor of conventional and novel PKCs), we examined N-formyl-methionyl-leucyl-phenylalanine (FMLP)- or 4-phorbol 12-myristate 13-acetate (PMA)-evoked superoxide anion (O(2)(-)) generation. Induced PKC translocation was characterized using confocal laser scanning microscopy.


RESULTS
The PKC zeta inhibitor significantly blocked FMLP- or PMA-induced O(2)(-) generation by eosinophils. However, this inhibitor attenuated PMA- but not FMLP-induced O(2)(-) generation by neutrophils. In contrast, Bis I inhibited FMLP-induced O(2)(-) generation by eosinophils and neutrophils in a similar manner. The PKC eta inhibitor had no significant effect, since both cell types lack PKC eta; this confirmed specificity of PKC zeta inhibitor effects. Finally, the translocation of PKC zeta to the plasma membrane induced by FMLP in both eosinophils and neutrophils was started at 1 min while the translocation was maintained for 15 min in eosinophils but not in neutrophils.


CONCLUSIONS
An atypical PKC, PKC zeta, regulates human eosinophil and neutrophil functions in a differential manner.
Kato
Masahiko
M
Department of Allergy and Immunology, Gunma Children's Medical Center, Hokkitsu, Japan. mkato@gcmc.pref.gunna.jp
Yamaguchi
Takafumi
T
Tachibana
Atsushi
A
Kimura
Hirokazu
H
D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D018613:Microscopy, Confocal; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099221:Protein Kinase C zeta
D004791:Enzyme Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D000099221:Protein Kinase C zeta