Endothelial monocyte-activating polypeptide-II (EMAP-II): a novel inducer of lymphocyte apoptosis.
The novel, proinflammatory cytokine endothelial monocyte-activating polypeptide-II (EMAP-II) was first found in tumor cell supernatants. EMAP-II is closely related or identical to the p43 auxiliary protein of the multisynthase complex, which is involved in protein synthesis. In vitro, EMAP-II induces procoagulant activity, increased expression of E- and P-selectins and tumor necrosis factor receptor-1, and ultimately, programmed cell death (apoptosis) in cultured endothelial cells. EMAP-II is also chemotactic for monocytes and neutrophils. However, the role of the p43/EMAP-II cytokine form in tumors is not understood. We hypothesized an immune-regulatory role within neoplastic tissues and investigated its effects on lymphocytes. EMAP-II causes a dose-dependent inhibition of proliferation and apoptosis in Jurkat T cells and mitogen-activated peripheral blood mononuclear cells. Coculture with DLD-1 colorectal cancer cells or media conditioned by these cells induces apoptosis in Jurkat cells, which is partially reversed by antibodies against EMAP-II. Our data suggest that EMAP-II constitutes a component of a novel, immunosuppressive pathway in solid tumors, which is not normally expressed outside the cell but in tumors, may be subject to abnormal processing and released from tumor cells.
Wolfson Digestive Disease Centre, University Hospital, University of Nottingham, Nottingham, UK. cliff.murray@nott.ac.uk
J C
JC
Murray
Y M
YM
Heng
P
P
Symonds
K
K
Rice
W
W
Ward
M
M
Huggins
I
I
Todd
R A
RA
Robins
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology*; D009363:Neoplasm Proteins / Q000494:pharmacology / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1