Age-Related Alterations in Basal Expression and in vitro, Tumour Necrosis Factor Alpha Mediated, Upregulation of CD11b

Abstract

Background: The β_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-α) 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-α 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-α 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-α was significantly higher in the elderly groups. Regression analysis showed a significant association between TNF-α and expression of CD11b on lymphocytes before and after TNF-α 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.

BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors

“…However in general, there is a dearth of information about neutrophil function with respect to ageing, and what information is available has been somewhat contradictory and difficult to interpret [6-8]. Some groups have reported similar findings to those of the BELFAST study in that centenarians seem to have better neutrophil function compared to those in the 'younger' old groups [9], and normal chemotaxis has been associated with better survival [10]. However neutrophil immunology has been relatively under researched and much further work requires to be carried out in this area.…”

Cytokine Expression and Production Changes in Very Old Age

“…In a Danish study, high levels of TNF-α were seen in centenarians and octogenarians with atherosclerotic CVD (Bruunsgaard et al 2000;, and elevated TNF-α was associated with mortality (Bruunsgaard et al 2003b). An age-related increase in plasma TNF-α was reported in Senieur-recruited BELFAST octo-/nonagenarian subjects (Armstrong et al 2001).…”

Blood pressure and TNF-α act synergistically to increase leucocyte CD11b adhesion molecule expression in the BELFAST study: implications for better blood pressure control in ageing

“…Recruitment was slow because subjects were elderly with a mean age of 85 years, were community living and relatively few could meet both the ‘elite’ criteria of the BELFAST (Rea et al 1997, 2009) and the exacting demands of the Senieur protocol for immune-gerontological studies (Ligthart et al 1984). The subject group enrolled from within the ongoing BELFAST study was also subject to time constraints imposed by the completion of a master’s research project (Armstrong et al 2001). Findings, therefore, need to be replicated by other groups.…”

“…This study was parallel to but part of the ongoing main BELFAST study. Elderly subjects were recruited with the criteria of the Senieur protocol (Ligthart et al 1984) and within the time constraint of a master’s research project on age-related change in CD11b/CD18 integrin expression (Armstrong et al 2001). The Senieur protocol, developed in the framework EURAGE (Concerted Action Programme on Ageing in the European Community) established exacting admission criteria for human immunogerontological studies, based on clinical and laboratory information (Ligthart et al 1984).…”

“…Cells were labelled with anti-CD11b and evaluated as described previously (Armstrong et al 2001). Whole blood, incubated for 1 h at 37°C, without prior addition of TNF-α served as a negative control to stimulation procedures.…”