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Functional changes in aging polymorphonuclear leukocytes
K Tanji-Matsuba1, S F van Eeden, Y Saito
1University of British Columbia, Pulmonary Research Laboratory, St Paul's Hospital, Vancouver, Canada.
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.
Insights
As immune cells age, polymorphonuclear neutrophils (PMN) show reduced function. Older PMN with low L-selectin display impaired actin assembly and migration, indicating significant functional changes during circulation.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Previous research indicated L-selectin expression decreases on aging polymorphonuclear neutrophils (PMN).
- Aging PMN exhibit fragmented DNA and morphological signs of apoptosis.
Purpose of the Study:
- To compare functional capabilities of PMN with low L-selectin (L-selectin[low]) versus the total PMN population.
- To investigate the impact of aging on PMN function in circulation.
Main Methods:
- Isolated L-selectin[low] PMN and compared them to L-selectin[mixed] PMN.
- Assessed filamentous actin (F-actin) assembly, cell shape change, deformability, migration, CD18 upregulation, and hydrogen peroxide production after stimulation with n-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP).
Main Results:
- L-selectin[low] PMN showed impaired F-actin assembly and shape change upon fMLP stimulation.
- Decreased deformability and migration capacity were observed in L-selectin[low] PMN.
- Enhanced CD18 upregulation and hydrogen peroxide production were noted in L-selectin[low] PMN.
Conclusions:
- PMN undergo significant functional alterations as they age in circulation.
- L-selectin expression level is a marker for age-related functional changes in PMN.