Monocytes recruited to sites of inflammation express a distinctive proinflammatory (P) phenotype

Abstract

Only a minor proportion of monocytes responds to chemoattractants. To test the possibility that chemoattractant-responsive monocytes have distinctive functional characteristics, we enriched or depleted monocyte preparations for cells having a proinflammatory (P) phenotype and tested their responses to biologically relevant chemoattractants. We prepared monocyte subpopulations by one of three independent techniques to minimize the chances of artifacts: 1) depletion of P monocytes by adherence to fibronectin; 2) enrichment for P monocytes by negative selection for HLA-DR antigen; and 3) flow cytometric sorting. We measured responsiveness of monocyte subpopulations to N-formyl-Met-Leu-Phe, C5a, zymosan-activated serum, and monocyte chemoattractant protein-1 by three parameters: 1) polarization, 2) actin polymerization, and 3) directed migration. With each chemoattractant and each parameter, there was a striking direct relationship between the responsiveness of the monocyte preparations and their content of P monocytes. Our data indicate that the capacity of monocytes to be recruited rapidly from the vasculature into sites of inflammation is a property of a subpopulation of monocytes with a distinctive, neutrophil-like proinflammatory phenotype.