Chemotactic and stimulating effect of tuftsin and its analogues on human monocytes

Abstract

Tuftsin, known for its phagocytosis stimulating capacity was examined for its chemotactic activity using a MN cell migration assay based on the Boyden technique. Tuftsin functioned as a chemotactic agent for MN cells in a dose-dependent way with highest activity detected in the concentration range of 50–200 μg/ml tetrapeptide. Pre-incubation of monocytes with tuftsin enhanced locomotion in tests of both random migration and leucotaxis. Structure-activity studies were carried out with [Ala 1]-, [Ser 1]-, [D-Ser 1]-, [Phe 3]-, [Phe 4]-, [D-Ala 4]- and [Glu 4]-analogues. Chemotactic activity seemed to be correlated with the presence of the [Thr 1]-residue, while the [Phe 3]- and [D-Ala 4]-analogues exerted significant activity. The stimulation of cell locomotion after pre-incubation of the cells with tuftsin proved less sensitive towards variations in the amino acid sequence. All analogues stimulated chemotaxis, except the [Glu 4]-derivative, while random migration was stimulated by [Phe 3]-, [Phe 4]- and [D-Ser 1]-tuftsin. These analogue studies indicated that chemotaxis and random migration can be influenced by different chemical structures.