An atypical protein kinase C, PKC zeta, regulates human eosinophil effector functions.
Protein kinase (PK) C comprises a family of isoenzymes that play key roles in downstream signalling and cell functions. We studied PKC zeta participation in the effector functions of human eosinophils stimulated with platelet-activating factor (PAF) or complement (C) 5a. After pretreating eosinophils with a myristoylated specific PKC zeta inhibitor; bisindlolylmaleimide I (BisI), an inhibitor of conventional and novel PKCs; or rottlerin, a PKC delta inhibitor, we examined PAF- and C5a-evoked functions. Induced PKC translocation was characterized by confocal laser scanning microscopy. The PKC zeta inhibitor blocked PAF- or C5a-induced eosinophil superoxide anion generation as effectively as BisI or rottlerin. The PKC zeta inhibitor also attenuated PAF- or C5a-induced eosinophil degranulation and adhesion. In contrast, the PKC zeta inhibitor did not affect PAF- or C5a-induced CD11b expression. Finally, both eosinophil shape changes and the translocation of PKC zeta and p47phox, a component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, to the plasma membrane induced by PAF or C5a were completely inhibited by the PKC inhibitor. Thus, the atypical PKC zeta regulates human eosinophil adhesion and effector functions.
Kato
Masahiko
M
Department of Allergy and Immunology, Gunma Children's Medical Centere, Hokkitsu, Japan. mkato@gcmc.pref.gunma.jp
Yamaguchi
Takafumi
T
Tachibana
Atsushi
A
Suzuki
Masato
M
Izumi
Takashi
T
Maruyama
Kenichi
K
Hayashi
Yasuhide
Y
Kimura
Hirokazu
H
D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D018613:Microscopy, Confocal; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D000099221:Protein Kinase C zeta
D039481:CD11b Antigen; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D019255:NADPH Oxidases; D010750:Phosphoproteins; D011493:Protein Kinase C; D013481:Superoxides; D000099221:Protein Kinase C zeta; C015482:protein kinase modulator; C060505:neutrophil cytosolic factor 1