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Age-related alterations in basal expression and in vitro, tumour necrosis factor alpha mediated, upregulation of
M E Armstrong1, H D Alexander, J L Ritchie
1School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland.
Background:
The beta(2-)integrin CD11b (Mac-1) plays a crucial role in the firm attachment of leucocytes to the endothelium during the inflammatory response.
Objective:
This study aimed to determine whether the increased incidence of infections witnessed in elderly individuals compared to their younger counterparts was associated with deficiencies in basal expression and/or upregulation of CD11b.
Methods:
Flow cytometry was used to measure CD11b expression, before and after in vitro tumour necrosis factor alpha (TNF-alpha) stimulation, on neutrophils, monocytes and lymphocytes from healthy volunteers aged less than 36 years and Senieur-approximated 70-85 and over 85 year olds. The TNF-alpha levels in serum were measured using a commercially available enzyme-linked immunoassay technique.
Results:
The basal expression of CD11b on monocytes and lymphocytes was highest in the 70-85-year-olds and lowest in the > 85-year-olds. Following in vitro stimulation using low (10 IU) and high (100 IU) TNF-alpha concentrations, subjects > 85 years consistently showed significantly lower increases in CD11b expression on each of the three cell types. The maximal increase in CD11b expression was in the 70-85-year age group for neutrophils and monocytes and in < 36-year-olds for lymphocytes. Serum TNF-alpha was significantly higher in the elderly groups. Regression analysis showed a significant association between TNF-alpha and expression of CD11b on lymphocytes before and after TNF-alpha stimulation and for neutrophils before stimulation.
Conclusions:
The results of this study suggest that CD11b expression on leucocytes may not be consistent throughout life. Such age-related changes could compromise the inflammatory response, rendering individuals > 85 years old more susceptible to infections. Alternatively, the lower levels of CD11b expression in this group may represent downregulation and protection against excess leucocyte activation within the vascular system and may, therefore, provide a mechanism for successful ageing.