| Project/Area Number |
16580243
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Basic veterinary science/Basic zootechnical science
|
|---|
| Research Institution | Yokohama City University |
|---|
Principal Investigator |
ARATANI Yasuaki Yokohama City University, Kihara Institute for Biological Research, Associate Professor, 木原生物学研究所, 準教授 (30192470)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Hideki Yokohama City University, Kihara Institute for Biological Research, Professor, 教授 (40085626)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | neutrophil / reactive oxygen species / infection / inflammation / apoptosis |
|---|
| Research Abstract |
The first study investigated the role of myeloperoxidase (MPO) in defense against Cryptococcus neoformans in a MPO-deficient (MPO-KO) mouse model. The survival of MPO-KO mice infected with C.neoformans was lower than that wild-type. The MPO-KO mice had significantly larger lung fungal burdens than wild-type mice. On day 7,MPO-KO mice showed a weak Th1 response to C.neoformans. The MPO-KO mice showed more severe pneumonia than wild-type, which was associated with the increase in the levels of IL-1α/β in the lungs. In MPO-KO mice, the pulmonary infection disseminated to the brain with occasional meningitis. KC level in the brain of infected MPO-KO mice was higher than that of control mice. These data suggest a major role of MPO in the response to cryptococcal infection.
The second study examined the role of neutrophil-derived ROS in neutrophil recruitment into ultraviolet B (UVB)-exposed skin of mice. UVB exposure of mice deficient in MPO, NADPH oxidase, or both, caused skin neutrophil in
… More
filtration peaking at 60, 48, and 48 h, respectively, which was earlier than the 72-h peak in wild-type mice. MIP-2 level was higher in mutant than wild-type. Neutrophil migration toward a localized source of KC was higher in mutant than wild-type. These results suggest that ROS produced by neutrophils regulate expression of MIP-2 and migration of neutrophils toward KC. This may explain the earlier infiltration of mutant neutrophils in response to UVB.
Stimulation of normal mouse neutrophils with phorbol 12-myristate 13-acetate (PMA) resulted in an acceleration of chromatin condensation and phosphatidylserine externalization that was not associated with caspase-3 activation. Caspase-independent death was completely inhibited by specific inhibitors for protein kinase C and p38 mitogen-activated protein kinase (p38MAPK), respectively. Activation of p38 MAPK is regulated by protein kinase C. On the other hand, cell death was abolished in NADPH oxidase-deficient neutrophils. p38 MAPK was activated by PMA in normal and MPO-KO neutrophils, whereas no activation was observed in NADPH oxidase-deficient neutrophils. These results strongly suggest that activation of p38 MAPK is regulated by endogenously generated superoxide or its metabolites other than HOCl. Less
|
