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THE BIOLOGICAL ACTIVITY OF NEW TUFTSIN DERIVATIVES - INDUCTION OF PHAGOCYTOSIS.

Anna Wardowska 1Krystyna Dzierzbicka 2Andrzej Myśliwski 1

1. Medical University of Gdańsk, Department of Histology and Immunology, Dębinki 1, Gdańsk 80-210, Poland
2. Technical University of Gdańsk, Department of Organic Chemistry, Narutowicza 11/12, Gdańsk 80-952, Poland

Abstract

Phagocytosis is one of the essential arms of host defense against bacterial or fungal infections. The phagocytic process consists of several major stages: 1. chemotaxis - migration of phagocytes to inflammatory sites, 2. attachment of particles to the surface of phagocytes, 3. ingestion - phagocytosis and intracellular killing of by oxygen-dependent and oxygen-independent mechanisms. This process can be induced by many phagocytosis stimulating factors. One of them is an endogenous tetrapeptide - tuftsin, that occurs in the blood of humans including human beings. Being an integral part of a heavy chain of IgG, tuftsin is liberated by the action of two specific enzymes: splenic tuftsin endocarboxypeptidase and leukokininase. Tuftsin is capable of potentiating granulocyte and macrophage functions such as: phagocytosis, motility, chemotaxis as well as bactericidal and tumoricidal activity. Due to high plasma instability of tuftsin, many derivatives of this peptide has been already synthesized and examined. Some of them are equally active as tuftsin or even display better biological properties.

The other particle able to induce phagocytosis is muramyl dipeptide (MDP) the smallest synthetic glycopeptide of bacterial origin that possesses an immunogenic activity. MDP is known to affect most functions of macrophages. The activation of those cells results mainly in increased reduction of oxygen to the superoxide anion (O2-) and then to hydrogen peroxide, which is involved in phagocytosis.

The aim of this study was to evaluate the impact of new tuftsin and MDP derivatives (one tuftsin analogue and four conjugates of tuftsin and muramyl dipeptide or nor-muramyl dipeptide) on the induction of the phagocytosis process through the influence on the activity of phagocytic cells.

We tested phagocytosis stimulating properties of a new group of derivatives on the peripheral blood mononuclear cells (PBMC) isolated from the venous blood of healthy, young donors. We performed Phagotest®, which enables the qualification of phagocytic activity of monocytes and granulocytes in heparinized whole blood.

The results of the study show that newly synthesized derivatives of tuftsin and MDP may influence the first step of immune response. Increased phagocytic activity of neutrophils and monocytes indicate that the examined compounds can be useful in curing bacterial infections.

 

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Presentation: Oral at V Multidyscyplinarna Konferencja Nauki o Leku, by Anna Wardowska
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-01-30 17:25
Revised:   2009-06-07 00:44