TY - JOUR
T1 - Inhibition of stimulus-specific neutrophil superoxide generation by alpha-tocopherol
AU - Kanno, Tomoko
AU - Utsumi, Toshihiko
AU - Kobuchi, Hirotsugu
AU - Takehara, Yoshiki
AU - Akiyama, Jitsuo
AU - Yoshioka, Tamotsu
AU - Horton, Alan A.
AU - Utsuml, Kozo
N1 - Funding Information:
This work was supported by funds from the Japan Keirine Association and the Eisai Co. We thank Mrs Hiroko Nakahara for her excellent technical assistance.
PY - 1995
Y1 - 1995
N2 - Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of αtocopherol, inhibited the superoxide (O2-) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myristate 13-acetate (PMA). ID50 for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1μM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 μM). The αtocopherol sensitive O2- generation was also observed in neutrophils induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by αtocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The αtocopherol content of RPMN was 12 ng/106 cells and a linear increase to 200 ng/106 cells by addition of αtocopherol to the cell suspension corresponded with an increased inhibition of O2- generation. These results indicate that both the chemical structure and the content of αtocopherol might be important factors in O2- generation by neutrophils.
AB - Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of αtocopherol, inhibited the superoxide (O2-) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myristate 13-acetate (PMA). ID50 for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1μM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 μM). The αtocopherol sensitive O2- generation was also observed in neutrophils induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by αtocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The αtocopherol content of RPMN was 12 ng/106 cells and a linear increase to 200 ng/106 cells by addition of αtocopherol to the cell suspension corresponded with an increased inhibition of O2- generation. These results indicate that both the chemical structure and the content of αtocopherol might be important factors in O2- generation by neutrophils.
KW - Protein kinase C inhibitor
KW - αtocopherol
UR - http://www.scopus.com/inward/record.url?scp=0029060482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029060482&partnerID=8YFLogxK
U2 - 10.3109/10715769509147551
DO - 10.3109/10715769509147551
M3 - Article
C2 - 7633571
AN - SCOPUS:0029060482
SN - 1071-5762
VL - 22
SP - 431
EP - 440
JO - Free Radical Research
JF - Free Radical Research
IS - 5
ER -