ABSTRACT
Studies have suggested that tumors are capable of modulating dendritic cell (DC) phenotype. A soluble protein produced by certain tumors, endothelial monocyte-activating polypeptide II (EMAP II) has been suggested as an anti-tumor agent based on its anti-angiogenic activity. However, this factor has not been evaluated for effects on DC. In this study, we analyzed the effect of Meth A fibrosarcoma supernatant and recombinant human EMAP II on DC migration. This included the migration of Langerhans cells from mouse ear skin sections and the migration of cells of a dendritic cell line (JAWS II) in a transwell culture system. The results of these studies indicated that EMAP II stimulates the migration of DC. Additional studies showed that the presence of the ascites form of the Meth A tumor led to a decrease in Langerhans cell (LC) numbers in the skin, and this decrease could be partially blocked by neutralizing antibody specific for EMAP II. Subcutaneous injection at the base of the ear of recombinant human EMAP II also led to a decrease in epidermal LC similar to that observed in tumor bearing mice. Together, these results suggest novel roles for EMAP II in modulating the migration of DC and suggest that these effects may modify Meth A tumor/host interactions.
Subject(s)
Antigens, Neoplasm/metabolism , Cell Movement/physiology , Cytokines/metabolism , Dendritic Cells/physiology , Fibrosarcoma/metabolism , Histocompatibility Antigens/metabolism , Neoplasm Proteins/metabolism , RNA-Binding Proteins/metabolism , Animals , Dendritic Cells/cytology , Female , Fibrosarcoma/pathology , Growth Inhibitors/metabolism , Humans , Mice , Mice, Inbred BALB C , Recombinant Proteins/genetics , Recombinant Proteins/metabolismABSTRACT
Tuatara are the sole survivors of an entire order of reptiles that thrived during the age of the dinosaurs. Therefore, knowledge of their physiology is critical to understanding the phylogeny of reptiles. Previous studies of the immune system of the tuatara did not assess T cell function. We analyzed T cell function among six captive tuatara by assessing concanavalin A (Con A), phytohemagglutinin (PHA) and mixed lymphocyte reaction (MLR) induced T cell proliferation. Peripheral blood mononuclear cells from six out of six and four out of four tuatara tested exhibited significant proliferative responses to Con A and PHA, respectively, as measured by an MTT reduction assay. A lower level of proliferation was detected in an MLR. However, Con A activated lymphocytes were not cytotoxic for a xenogeneic murine mastocytoma cell line (P815).
Subject(s)
Reptiles/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes/immunology , Animals , Cell Proliferation , Concanavalin A/immunology , Female , Lymphocyte Activation/immunology , Lymphocyte Culture Test, Mixed , Male , Phytohemagglutinins/immunology , T-Lymphocyte Subsets/cytologyABSTRACT
We examined the effect of 17alpha-ethinylestradiol on immunity of the Western fence lizard, Sceloporus occidentalis. Injection of 17alpha-ethinylestradiol resulted in dose-dependent suppression of peripheral blood leukocyte levels as determined by cell counts, whereas total spleen cell levels were decreased only at higher doses of 17alpha-ethinylestradiol. In contrast, spleen cell proliferation was enhanced by 17alpha-ethinylestradiol as measured by reduction of MTT to formazan following a two-way mixed lymphocyte reaction. Antibody responses were unaffected. Effects on peripheral blood leukocyte levels and spleen cell proliferation similar to those observed in response to injection of 17alpha-ethinylestradiol were observed following injection of a single dose of hydrocortisone. However, injection of lizards with 17alpha-ethinylestradiol did not result in a significant increase in serum cortisol. Results of this study suggest that exposure of Western fence lizards to 17alpha-ethinylestradiol leads to decreased numbers of circulating leukocytes and total spleen cell numbers and the enhancement of spleen cell proliferation in a two-way mixed lymphocyte reaction. These effects probably involve mechanisms other than or in addition to the induction of cortisol release.
