David Green, MD, PhD

Neutrophils were less chemotactic and migrated with less accuracy in older versus younger healthy persons.

Immunological senescence refers to the diminishing effectiveness of the immune system with age. Although impairment of T- and B-cell activity has been well-described, the impact of aging on neutrophil function has been underappreciated. Now, U.K. investigators have assessed the effect of age on the migration of neutrophils toward chemotactic targets in 70 healthy individuals aged 21 to 89 years.

Neutrophils from older persons were found to be less chemotactic and to migrate with less accuracy than neutrophils from younger persons, whether the target was a chemokine (CXCL8) or sputum from patients with Streptococcus pneumoniae–associated pneumonia. Chemotaxis declined gradually after age 30, but was significantly reduced after age 60 (mean difference between persons aged 60–69 vs. 21–29, 1.25 µm/mi; P=0.02).

To determine the cause of the impaired chemotaxis, the researchers assessed levels of phosphorylated phosphoinositide 3-kinase (PI3K) activity. Basal activity of this enzyme was low in neutrophils of young individuals but was increased in response to CXCL8, blocking PI3K-inhibited migration. In contrast, basal PI3K activity was high in neutrophils of older persons, but failed to increase further after exposure to CXCL8, and inhibition of the enzyme improved chemotaxis. The plasma concentration of another neutrophil enzyme, elastase, was also increased in older versus younger donors (17.3 nM vs. 7.5 nM; P=0.006); evidence of primary granule release was also found.

Citation(s):

Sapey E et al. Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: Toward targeted treatments for immunosenescence. Blood 2014 Jan 9; 123:239.