A DISCRETE SUBPOPULATION OF HUMAN MONOCYTES EXPRESSES A NEUTROPHIL-LIKE PROINFLAMMATORY (P) PHENOTYPE

We have demonstrated that a discrete and naturally occurring subpopula tion of human monocytes expresses a neutrophil-like proinflammatory (P ) phenotype. P monocytes constitute 20-30% of the circulating monocyte pool and are characterized by 1) avid adherence to extracellular matr ix through high-level cell-surface expression of alpha(5-), beta(1-), and beta(2)-integrins; 2) high capacity to produce reactive oxygen spe cies; 3) high content of serine proteinases and alpha(1)-proteinase in hibitor; and 4) proteolytic activity against a soluble peptide human l eukocyte elastase substrate, [H-3]elastin, and solid-phase fibronectin , even in the presence of proteinase inhibitors. However, P monocytes express little or no cell-surface HLA-DR antigen, suggesting that they are unable to participate in specific immune responses. In contrast, the remainder of circulating monocytes have a low proinflammatory pote ntial but contain the population of monocytes with high-level expressi on of HLA-DR antigen. P monocytes can readily be separated from the re mainder of monocytes on the basis of 1) their capacity to adhere to fi bronectin; and 2) their absent expression of HLA-DR antigen when flow cytometry or immunomagnetic beads are used. Our data indicate that, wh en recruited to sites of inflammation, P monocytes can either promote resolution of inflammation or contribute to tissue injury.