Generation of human innate immune responses towards membrane macrophage colony stimulating factor (mM-CSF) expressing U251 glioma cells within immunodeficient (NIH-nu/beige/xid) mice.
The response of human peripheral blood mononuclear cells (PBMC) to cloned human HLA-A2+ U251 glioma cells (U251-2F11/TK) expressing membrane macrophage colony stimulating factor (mM-CSF) was investigated in vitro and in vivo. Enriched human monocytes derived from cancer patients produced a respiratory burst following 20min of interaction with mM-CSF expressing U251 glioma cells. This respiratory burst response was not observed in the enriched human monocytes following similar exposure to the viral vector control U251 (U251-VV) cells. Reactive oxygen species such as H(2)O(2) and HOCl produced death of the U251 cells. The U251-2F11/TK cells failed to grow in severely compromised combined immunodeficient (NIH-bg-nu-xidBR) mice that were depleted of murine monocyte/macrophages then reconstituted with human HLA-A2+ PBMC. Reactive oxygen species (ROS) were produced by PBMC, both in vitro and in vivo in response tomM-CSF expressing U251 cells. U251-2F11/TK cells failed to form subcutaneous tumors in macrophage depleted mice reconstituted with human PBMC; whereas, progressive growth of such tumors was observed with the U251-VV cells. U251-2F11/TK tumors formed if the initial inoculums of PBMC were depleted of monocytes. From this work it can be concluded that mM-CSF transduced U251-2F11/TK glioma cells can safely stimulate human innate immune responses in vivo.
Delgado
Christina
C
Department of Diagnostic and Molecular Medicine, Box 113, Veterans Affairs Medical Center, 5901 E. 7th Street, Long Beach, CA 90822, USA.
Hoa
Neil
N
Callahan
Linda L
LL
Schiltz
Patric M
PM
Jahroudi
Reza Alipanah
RA
Zhang
Jian Gang
JG
Wepsic
H Terry
HT
Jadus
Martin R
MR
D000818:Animals; D045744:Cell Line, Tumor; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D016897:Respiratory Burst; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor