Investigation of monocyte chemoattractant protein-1 (MCP-1)

Abstract

Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry (Oral Biology)Includes bibliography (leaves 54-66)Mononuclear phagocytes play a critical role in defending the host against foreign organisms and in regulating the behavior of other cells. A characteristic feature of macrophages is their ability to infiltrate tumors. Human malignant cells secrete low molecular size proteins that attract peripheral blood monocytes and may be responsible for the accumulation of tumor associated macrophages observed in vivo. One such chemoattractant, monocyte chemoattractant protein-1 is produced by smooth muscle cells and a human glioma cell line. Monocyte chemotactic factors produced by different malignant cell types were isolated by immunoprecipitation and then monocyte chemotactic activity was assayed. The results demonstrated that nine of thirteen human malignant cell lines synthesized detectable levels of MCP-1. In each case the chemotactic activity was completely inhibited by MCP-1 antisera. The four cell lines in which there were no detectable levels of MCP-1 in immunoprecipitation experiments also did not produce chemotactic activity. The results demonstrated the correlation between the production of monocyte chemotactic activity and the synthesis of MCP-1. Therefore, the predominant monocyte chemoattractant produced by tumor cells of differing origin are related to MCP-1. [TRUNCATED