Effect of the C-terminal domain peptide fragment (65-76) of monocytic chemotactic protein-1 (MCP-1) on the interaction between MCP-1 and heparin.

摘要

Monocytic chemotactic protein-1 (MCP-1) belongs to the CC chemokine family controlling leu- kocyte migration to the focus of inflammation [1, 2]. Chemokines take part in different stages of the athero- sclerotic plaque formation, MCP-1 playing a signifi- cant role in the process [3]. Much attention is paid to the development of chemokine action inhibitors, especially to peptide inhibitors [4] and MCP-1 mutant variants [5, 6]. In addition to high-affinity binding between chemokines and membrane receptors of the target cells, low-affinity binding between chemokines and glycosaminoglycans (GAGs) is necessary for the leukocyte migration from the blood to the lesion zone. Heparin and heparan sulfate from the extracellular matrix are the main GAGs binding with chemokines [7]. Previously, we obtained an original peptide, a fragment of the MCP-1 C-terminal domain (65–76, H–Asp–His- Leu–Asp–Lys–Gln–Thr–Gln–Thr–Pro–Lys–Thr– OH termed peptide X or PX; hereinafter referred to as the peptide), which diminished in vitro migration of monocytes and had anti-inflammatory properties in vivo [8, 9].