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.
Murray
J C
JC
Wolfson Digestive Disease Centre, University Hospital, University of Nottingham, Nottingham, UK. cliff.murray@nott.ac.uk
Heng
Y M
YM
Symonds
P
P
Rice
K
K
Ward
W
W
Huggins
M
M
Todd
I
I
Robins
R A
RA
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