FORMATION OF EOSINOPHIL EXTRACELLULAR TRAP INDUCED BY LYSOPHOSPHATIDYLSERINE AND ACTIVATED PLATELETS
- Title
- FORMATION OF EOSINOPHIL EXTRACELLULAR TRAP INDUCED BY LYSOPHOSPHATIDYLSERINE AND ACTIVATED PLATELETS
- Other Titles
- 리소포스파티딜세린 및 활성화된 혈소판에 의해 유도된 호산구 세포외 덫에 관한 연구
- Author
- 김혜정
- Alternative Author(s)
- 김혜정
- Advisor(s)
- 정일엽
- Issue Date
- 2021. 2
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
-
Eosinophils are crucial effector cells that play a role in host defense against parasitic
infection and allergic inflammatory diseases, largely through release of cytotoxic granule
proteins and interaction with other immune and nonimmune cells. Recent evidence
demonstrates that activated eosinophils undergo eosinophil extracellular trap (EET), the
extracellular release of threads of decondensed chromatin decorated with histones and cell
free granules, which is also accompanied by loss of membrane integrity and cell viability.
EET has been implicated in inflammatory immune responses in asthmatic airways. Platelets
are tiny fragments of cells that are essential for normal blood clotting. Beyond central role
in hemostasis, platelets have increasingly been appreciated as immune cells that have a role
in inflammation through interactions with other leukocytes and through release of soluble
mediators and membrane-bound small particles, including platelet-derived microparticles
(PMPs). Mounting evidence have propose bidirectional interactions between eosinophils
and platelets in response to inflammatory responses. We recently demonstrated that human
eosinophils selectively and abundantly express P2Y10, a G protein-coupled receptor, which
binds a bioactive lipid mediator, lysophosphatidylserine (LysoPS).
In the first series of experiments, we aimed to probe a function of LysoPS in eosinophils.
we demonstrated that LysoPS induced EET formation accompanied by both lytic cell death
and degranulation. LysoPS-induced EET was independent to reactive oxygen species
production and irrelevant to several signaling pathways examined, but dependent on
protein arginine deiminase 4. Eosinophils from severe asthmatics exhibited greater
degranulation, but not EET formation, in response to LysoPS, than those from nonsevere
asthmatics, along with great expression of surface P2Y10. These results suggest that
LysoPS-dependent EET or degranulation plays a potential role in eosinophilic
inflammation of severe asthma.
In the second series of experiments, we examined whether activated platelets induced EET
formation. To this end, platelets were stimulated with a calcium ionophore A23187 and
platelet agonists thrombin and ADP and then fractionated to conditioned medium (CM) and
pellet. Our results showed that both CM and cell pellet from the A23187-, but not thrombin
or ADP-activated platelet cultures induced EET formation, suggesting that fully activated
platelets are capable of eliciting EET formation. The EET-inducing activities by CM and
pellet from the A23187-activated platelet cultures were proportional to the number of
activated platelets. Confocal microscopic analysis demonstrated that PMPs, as assessed by
CD41 expression, were entrapped in EET and aggregated around EET-undergoing
eosinophils, when platelets were activated with pellet from the A23187-activated platelet
cultures. Thus, platelet-eosinophil cross-talk modulates inflammatory responses through
EET formation.
Collectively, our results imply two important facets in EET, a newly emerging eosinophil
activity involved in host defense and inflammation. First, our identification of LysoPS as a
potent inducer of EET expands a repertoire of known inducers that is currently very limited.
Second, we for the first time show that fully activated platelets induce an appreciable
amount of EET, translating activation of platelets to the notable eosinophil activity, EET
- URI
- https://repository.hanyang.ac.kr/handle/20.500.11754/159535http://hanyang.dcollection.net/common/orgView/200000485543
- Appears in Collections:
- GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Theses (Ph.D.)
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