Anti-CCL23 monoclonal antibody, clone 204063

CCL23 [Ck beta 8-1/myeloid progenitor inhibitory factor 1 (MPIF1)/macrophage inflammatory protein-3 (MIP3)], a member of the CC chemokine family, is involved in leukocyte trafficking, and implicated in inflammatory diseases. In the present study, we investigated the role of CCL23 in the development of human atherosclerosis, which is characterized by an inflammatory disease. CCL23 transcripts were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and CCL23 protein by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Expression of adhesion molecules was determined by flow cytometry, and matrix metalloproteinase-2 (MMP-2) levels by zymography. Proatherogenic factors such as oxidized low-density lipoprotein (oxLDL) and oxidative stress markedly enhanced CCL23 release from human THP-1 macrophages. CCL23 stimulated chemotaxis of human THP-1 monocytes in a dose-dependent manner and enhanced the expression of adhesion molecule CD11c, as well as release of MMP-2 from the THP-1 monocytes. Moreover, CCL23 expression at the mRNA level was significantly higher in human atherosclerotic lesions than in normal arteries, and CCL23 protein was co-expressed with CD68, a specific marker for macrophages. Circulating levels of plasma CCL23 were higher in atherosclerotic patients than in normal subjects. These findings suggest that CCL23 plays a role in the development of human atherosclerosis. CCL23 may be a useful target for the development of antiatherogenic agents.

Human CCL23 (also known as CK beta 8. MPIF-1, or MIP-3) has been recently reported to induce endothelial cell migration and tube formation via CCR1. Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix and also appear to play critical roles in angiogenesis. In the present study, we have demonstrated that CCL23 enhances the expression of MMP-2 mRNA and protein levels in endothelial cells in a dose-dependent manner, but hits no effect on the expression levels of MMP-9, TlMP-1, TIMP2, and MT1-MMP. CCL23 was shown to dose-dependently activate the expression of the MMP-2/Lue reporter gene. thereby indicating that it stimulates the transcription of the MMP-2 gene. Vascular endothelial cells. when exposed to CCL23, showed it marked ability to invade through a 3D Matrigel. This increase in invasion was also correlated with enhancements in the expression and activity of MMP-2. Neutralization with anti-CCL23 and anti-CCR1 antibodies. its well as the heat-induced inactivation of CCL23, resulted in it blockage of the CCL23-activated invasion, indicating that the invasion of HUVECs was induced by CCL23 specifically. Futhermore, we showed that the CCL23-induced invasion was inhibited by MMP inhibitors such as GM6001 and a specific MMP-2 Inhibitor 1. Our results indicate that CCL23 may play a direct role in angiogenesis, via the upregulation of MMP-2 expression. (c) 2005 Elsevier Inc. All rights reserved.