TY - JOUR
T1 - ProNGF mediates death of Natural Killer cells through activation of the p75NTR-sortilin complex
AU - Rogers, Mary-Louise
AU - Bailey, Sheree
AU - Matusica, Dusan
AU - Nicholson, I
AU - Muyderman, Hakan
AU - Pagadala, Promila
AU - Neet, Kenneth
AU - Zola, Heddy
AU - MacArdle, Peter
AU - Rush, Robert
PY - 2010/9
Y1 - 2010/9
N2 - The common neurotrophin receptor P75NTR, its co-receptor sortilin and ligand proNGF, have not previously been investigated in Natural Killer (NK) cell function. We found freshly isolated NK cells express sortilin but not significant amounts of P75NTR unless exposed to interleukin-12 (IL-12), or cultured in serum free conditions, suggesting this receptor is sequestered. A second messenger associated with p75NTR, neurotrophin-receptor-interacting-MAGE-homologue (NRAGE) was identified in NK cells. Cleavage resistant proNGF123 killed NK cells in the presence of IL-12 after 20. h and without IL-12 in serum free conditions at 48. h. This was reduced by blocking sortilin with neurotensin. We conclude that proNGF induced apoptosis of NK cells may have important implications for limiting the innate immune response.
AB - The common neurotrophin receptor P75NTR, its co-receptor sortilin and ligand proNGF, have not previously been investigated in Natural Killer (NK) cell function. We found freshly isolated NK cells express sortilin but not significant amounts of P75NTR unless exposed to interleukin-12 (IL-12), or cultured in serum free conditions, suggesting this receptor is sequestered. A second messenger associated with p75NTR, neurotrophin-receptor-interacting-MAGE-homologue (NRAGE) was identified in NK cells. Cleavage resistant proNGF123 killed NK cells in the presence of IL-12 after 20. h and without IL-12 in serum free conditions at 48. h. This was reduced by blocking sortilin with neurotensin. We conclude that proNGF induced apoptosis of NK cells may have important implications for limiting the innate immune response.
KW - Apoptosis
KW - Natural Killer (NK) cells
KW - ProNGF (pro nerve growth factor)
KW - Sortilin
KW - TNFRSF (tumor necrosis factor receptor super family)
UR - http://www.scopus.com/inward/record.url?scp=77956340615&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2010.05.040
DO - 10.1016/j.jneuroim.2010.05.040
M3 - Article
SN - 0165-5728
VL - 226
SP - 93
EP - 103
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -