Functional Changes in Aging Polymorphonuclear Leukocytes

Abstract

Background —Previous studies from our laboratory have shown that the expression of L-selectin on polymorphonuclear neutrophils (PMN) decreases as the cell ages in the circulation and that these older PMN have more fragmented DNA and show morphological features of apoptosis. Methods and Results —The present study was designed to compare the functional capabilities of PMN expressing low levels of L-selectin (L-selectin low ) and the total population of PMN they were isolated from (L-selectin mixed ). The results show no difference of the baseline filamentous actin (F-actin) content between PMN expressing low and high levels of L-selectin. However, the ability of L-selectin low PMN to assemble F-actin was impaired after stimulation by n -formyl- l -methionyl- l -leucyl- l -phenylalanine (fMLP) (1 nmol/L fMLP: P <.02, 10 nmol/L fMLP: P <.01). The ability of L-selectin low PMN to change shape when stimulated (10 nmol/L fMLP) was also decreased ( P <.05). Filtration studies showed no difference in baseline deformability between L-selectin low and L-selectin mixed leukocytes, but the L-selectin low cells showed a decreased ability to stiffen after fMLP stimulation ( P <.05). L-selectin low cells demonstrated a decreased ability to migrate toward a chemoattractant (1, 3, and 10 nmol/L fMLP) ( P <.004) but have an enhanced ability to upregulate CD18 ( P <.00002) and produce hydrogen peroxide ( P <.00004). Conclusions —We conclude that PMN undergo substantial functional changes as they age in the circulation.