10/06/2008

Preliminar Immunomodulating Activities - P-MAPA effect in dendritic cells

 

• P-MAPA effect in dendritic cells development and maturation

 

Dendritic cells are considered the principal antigen presenting cells of the immune system, playing pivotal roles in the stimulation, regulation and development of immune response.

 

These cells originate from hematopoietic stem cells and migrate through out the blood flow to most body tissues. Dendritic cells in peripheral tissue are immature and upon encountering inflammatory mediators undergo maturation, acquiring the potential to induce potent immune responses.

 

In the non-lymphocyte tissues, they capture and transport antigens to the lymphocyte tissue, where interacting with other dendritic cells and T lymphocytes, they promote their activation and amplification of specific immune responses.

 

Immunomodulators represent a type of drug that have the capacity to amplify immune responses against infectious pathogens and tumor cells.

 

The crucial role of dendritic cells in the early immune response development and the capacity to interact with most types of immune cells indicated the possibility that the action of these new drugs could be directed to dendritic cells and through them an effective and prolonged immune response would be initiated.

 

The immunomodulator P-MAPA has been show to exert antiviral and antitumoral activities with non-toxic effects and the modulation of myelopoietic response in Ehrlich ascites tumor-bearing mice, leading to a significant increase in survival and tumor growth inhibition.

 

The purpose of this preliminary study is to investigate the ability of P-MAPA to stimulate the production of matured dendritic cells from peripheral blood monocytes.

 

The monocyte will be collected by density gradient centrifugation (Ficoll-Hypaque) with posterior plastic adherence. The culture will be maintained for seven days in a complete medium (RPMI with 10% fetal calf serum) with different concentrations of P-MAPA. After seven days the cells will be collected and the expression of differentiation and maturation cellular markers will be analyzed by flow citometry.

 

Results :

 

Preliminary analyses indicated that dendritic cells could differentiate from monocyte in culture with P-MAPA presenting specific DC markers similar to cultures supplemented with cytokines (GM-CSF and IL4).