Functional and metabolic heterogeneity among normal neutrophil subpopulations

Abstract

In this study, normal human peripheral blood neutrophils were separated into subpopulations by centrifugation on discontinuous Percoll density gradients and further characterized according to various functional and metabolic capabilities. Chemotaxis was measured in response to optimal concentrations (20 nM) of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). According to a population ratio analysis, the majority of cells that contain the highest proportion of fast migrating cells are isolated between the densities of 1.093 and 1.096 gm/ml. Arachidonic acid (AA) metabolism was also determined in neutrophil subpopulations. On initial density gradients, cells isolated from 1.084-1.087 gm/ml and incubated in the presence of exogenous [3H]AA produce 50% of the total [3H]LTB4 produced in response to ionophore A23187 stimulation; whereas after prelabeling with [3H]AA for 2 hr at 37 degrees C, the cells between 1.087 and 1.093 gm/ml are the most active at both releasing [3H]AA from the cellular phospholipids and synthesizing [3H]LTB4 (dpm/cell). These studies demonstrate the significant functional and metabolic heterogeneity that exists among normal neutrophil subpopulations.

Differences in oxidative response of subpopulations of neutrophils from healthy subjects and patients with rheumatoid arthritis.

“…2 Several chemotactic and inflammatory factors appear to recruit neutrophils to inflammatory foci,"8 and a feature of many of these mediators is their ability at low concentrations to prime neutrophils for increased production of superoxide anion when subsequently stimulated. From our own observations of neutrophil subpopulation heterogeneity914 and the studies of others, [15][16][17] we propose that within the circulating neutrophil pool, cells coexist at different levels of functional status. Consequently, neutrophil migration through vessel walls adjacent to inflammatory lesions may be selective for a hyperactive subpopulation that is highly responsive to priming agonists and stimulating agents.…”

Bimodal distribution of proteinase 3 (PR3) surface expression reflects a constitutive heterogeneity in the polymorphonuclear neutrophil pool

“…Various techniques of cell fractionation by density centrifugation or flow electrophoresis revealed physicochemical and functional heterogeneity in the circulating neutrophil pool [19][20][21]. Some of these variations concerned azurophil or specific granule components defining subpopulations of PMN with differences in myeloperoxidase or lactoferrin activity [22,23].…”