MONOCYTES RECRUITED TO SITES OF INFLAMMATION EXPRESS A DISTINCTIVE PROINFLAMMATORY (P) PHENOTYPE

Only a minor proportion of monocytes responds to chemoattractants. To test the possibility that chemoattractant-responsive monocytes have di stinctive functional characteristics, we enriched or depleted monocyte preparations for cells having a proinflammatory (P) phenotype and tes ted their responses to biologically relevant chemoattractants. We prep ared monocyte subpopulations by one of three independent techniques to minimize the chances of artifacts: 1) depletion of P monocytes by adh erence to fibronectin; 2) enrichment for P monocytes by negative selec tion for HLA-DR antigen; and 3) flow cytometric sorting. We measured r esponsiveness of monocyte subpopulations to N-formyl-met-Leu-Phe, C5a, zymosan-activated serum, and monocyte chemoattractant protein-1 by th ree parameters: 1) polarization, 2) actin polymerization, and 3) direc ted migration. With each chemoattractant and each parameter, there was a striking direct relationship between the responsiveness of the mono cyte preparations and their content of P monocytes. Our data indicate that the capacity of monocytes to be recruited rapidly from the vascul ature into sites of inflammation is a property of a subpopulation of m onocytes with a distinctive, neutrophil-like proinflammatory phenotype .