Secretion of Monocyte Chemoattractant Protein-1 (MCP-1) by Human Mononuclear Phagocytes

Abstract

The stage for the work that is presented here was set in a 1973 paper by Altman et al., entitled “A human mononuclear leukocyte chemotactic factor: characterization, specificity and kinetics of production by homologous leukocytes” (1). They reported that stimulation by tuberculin (PPD) of blood mononuclear leukocytes (PBMC’s) from individuals with a positive skin test to tuberculin caused production of a chemotactic factor for human monocytes. Since the factor was not produced by PPD-stimulated leukocytes from PPD-negative subjects, the authors suggested that it could account for recruitment of macrophages in delayed cutaneous hypersensitivity reactions. The factor was a heat stable macromolecule with a molecular mass, estimated by gel filtration, of about 12,500 daltons. Altman later referred to this molecule as leukocyte-derived chemotactic factor, or LDCF. In 1989, we reported the purification to homogeneity of the predominant chemotactic activity for monocytes in culture fluids of PHA-stimulated human mononuclear leukocytes We suggested that this 8700 dalton protein, which we call monocyte chemoattractant protein-1 (MCP-1), is the attractant described by Altman et al. In the interval since the last international meeting on chemotactic cytokines, we have developed a sandwich ELISA that can quantify the amount of MCP-1 in biological fluids (4). Using this assay, we find that PPD-stimulated PBMC’s from a tuberculin-positive human subject secrete large amounts of MCP-1 within 48 hrs. The amount is too much to be accounted for by secretion by the number of lymphocytes that react with specific antigen in this system. Therefore, MCP-1 must be secreted by non-immune cells -- lymphocytes or monocytes -- stimulated by the very low concentrations of a mediator released by PPD-reactive lymphocytes.