TY - JOUR
T1 - Re-organization of mitochondria at the NK cell immune synapse
AU - Abarca-Rojano, Edgar
AU - Muñiz-Hernández, Saé
AU - Moreno-Altamirano, María Maximina Bertha
AU - Mondragón-Flores, Ricardo
AU - Enriquez-Rincón, Fernando
AU - Sánchez-García, F. Javier
N1 - Funding Information:
We thank Sirenia González (Electron Microscopy Unit), Mónica Mondragón (Department of Biochemistry), and Iván Galvan (Confocal microscopy unit) from CINVESTAV, and María Esther Sánchez, and Oliver López (Electron Microscopy Unit) from ENCB-IPN, for their technical assistance and Olga Dominguez (Hospital de la Mujer, Blood Bank) for providing buffy coats. This work was supported by CONACYT (SEP-2003-CO2-44228) and CGPI-IPN (20070268) grants to FJSG. SMH was supported by a Ph.D. fellowship from CONACYT (169932). EAR, MMBMA and FJSG are COFAA, EDI and SNI fellows; RMF and FER are SNI fellows.
PY - 2009/1/29
Y1 - 2009/1/29
N2 - As part of the innate immune response NK cells destroy infected, transformed, or otherwise stressed cells within hours of activation. In contrast, CD4+ T lymphocytes require a sustained increase in their metabolism in order to cope with the biogenesis of cell components, in a process of proliferation and differentiation into effector cells. Recently, mitochondria have been implied in T lymphocyte immune synapse function but little is known on the role of mitochondria in the NK cell interaction with tumour cells. Here we analysed NK cells mitochondrial membrane potential (Δψm) as an indicator of mitochondrial energy status and cellular homeostasis. Upon contact with K562 tumour cells, NK cells undergo Δψm depolarization, indicating a rapid consumption of their metabolic energy. Furthermore, pharmacological inhibition of ATP synthesis down-regulates NK cell cytotoxic activity. Confocal- and electron-microscopy analyses showed re-organization of NK cells mitochondria towards the site of interaction with K562 tumour cell (NK cell immune synapse), perhaps as a way to compensate for local energy consumption. Interestingly, mitochondrial re-organization also takes place following NK stimulation with anti-NKGD2 antibodies but not with anti-KIR2DL1 antibodies, suggesting that activating rather than inhibiting cell signalling, triggered by NK cell receptors, is involved in NK cell mitochondria dynamics.
AB - As part of the innate immune response NK cells destroy infected, transformed, or otherwise stressed cells within hours of activation. In contrast, CD4+ T lymphocytes require a sustained increase in their metabolism in order to cope with the biogenesis of cell components, in a process of proliferation and differentiation into effector cells. Recently, mitochondria have been implied in T lymphocyte immune synapse function but little is known on the role of mitochondria in the NK cell interaction with tumour cells. Here we analysed NK cells mitochondrial membrane potential (Δψm) as an indicator of mitochondrial energy status and cellular homeostasis. Upon contact with K562 tumour cells, NK cells undergo Δψm depolarization, indicating a rapid consumption of their metabolic energy. Furthermore, pharmacological inhibition of ATP synthesis down-regulates NK cell cytotoxic activity. Confocal- and electron-microscopy analyses showed re-organization of NK cells mitochondria towards the site of interaction with K562 tumour cell (NK cell immune synapse), perhaps as a way to compensate for local energy consumption. Interestingly, mitochondrial re-organization also takes place following NK stimulation with anti-NKGD2 antibodies but not with anti-KIR2DL1 antibodies, suggesting that activating rather than inhibiting cell signalling, triggered by NK cell receptors, is involved in NK cell mitochondria dynamics.
KW - Cytotoxicity
KW - Mitochondria
KW - NK cells
UR - http://www.scopus.com/inward/record.url?scp=59849117077&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2008.10.008
DO - 10.1016/j.imlet.2008.10.008
M3 - Artículo
C2 - 19038287
SN - 0165-2478
VL - 122
SP - 18
EP - 25
JO - Immunology Letters
JF - Immunology Letters
IS - 1
ER -