ANTIGENIC HSP70 PEPTIDE COMPLEX UPREGULATE ALTERED EXPRESSION OF DOCKING RECEPTOR ICAM 1 IN TAMS INCREASES IN DALTONS LYMPHOMA BEARING MICE
P. K. Gautam
Department of zoology, Faculty of Science, Banaras Hindu University, Varanasi-221005, U.P., India
A. Acharya
Department of zoology, Faculty of Science, Banaras Hindu University, Varanasi-221005, U.P., India
Receiving Date:
2015-05-22
Acceptance Date:
2015-06-22
Publication Date:
2015-07-25
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Abstract
ICAM-1 facilitates docking between APC and T cell for cell-cell interaction and transmigration.
Tumor progression downregulate the expression of ICAM-1 from M1 phenotype of macrophages into M2
phenotype macrophages which promote tumor progression. It has been observed that Hsp70 preparations
derived from normal tissues do not elicit tumor immunity, while Hsp70 preparation from tumor cell able
to elicit tumor immunity due to tumor antigen association. In the present study it has been investigated
the function of Hsp70-peptide complex on TAMs in DL bearing host. For tumor system, healthy BALB/c
(H2d) strain of mice of either sex at 8–12 weeks of age was taken and 1.0 X 106 DL cells in 0.5 ml sterile
PBS were transplanted and obtained from ascitic fluid of DL-bearing mice. TAMs were harvested from
tumor bearing mice as peritoneal exudates cells (PECs) by adherent purification. Hsp70 peptide complex
was purified by peng et. al., 1998 method and hsp70 were used for treatment of cells. TAMs were treated
with 10µg/ml of Hsp70 peptide for 24 hrs and expression profiling of ICAM-1receptors were analysis by
Immunocytochemistry, western blotting, Flowcytometry and RT-PCR. Differences between groups were
detected by unpaired t-tests. It has been observed that in normal state of M1 phenotype of macrophage
the ICAM-1 expression was found (34.1±3.04) while in TAMs it was (9.0±1.2). Tumor progression
decreased the expression of docking receptor CD54 or ICAM-1 over M1 phenotype which facilitates
tumor progression by deactivation of cell mediated immune responses. Treatment of hsp70 peptide
resulted in significant increase ICAM-1 expression in both normal phenotypes of macrophages
(169±13.01) as well as TAMs (30.1±3.1) but it was at lesser extent as compare to macrophage.Therefore,
it can be concluded that exogenous application of tumor derived hsp70 peptide enhances the suppressed
ICAM-1 expression in Mɸ and TAMs, which provide further insight for DL-induced immunosuppression
in a tumor-bearing host. Hsp70 peptide might be helpful in designing a novel immunotherapeutic
vaccination approaches.
Keywords:
ICAM-1; Macrophages; TAMs; Tumor Progression; Hsp70-peptide complex; Immunotherapy.
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