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Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

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Related in: MedlinePlus

Representation of the differences in A) the expression of CX3CR1 on the classical (CLS), intermediate (INT) and non-classical (NON) monocyte subsets and B) the classical to intermediate monocyte ratio, between cases (grey) and controls (white) for dementia, diabetes mellitus and anemia.Comparison-wise p-value, **p<0.01, *p<0.05.
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pone-0104522-g003: Representation of the differences in A) the expression of CX3CR1 on the classical (CLS), intermediate (INT) and non-classical (NON) monocyte subsets and B) the classical to intermediate monocyte ratio, between cases (grey) and controls (white) for dementia, diabetes mellitus and anemia.Comparison-wise p-value, **p<0.01, *p<0.05.

Mentions: To determine whether the observed alterations to monocyte and DC frequency and monocyte CCR2 and CX3CR1 expression in the advanced-age, frail elderly are associated with chronic disease, we analyzed a larger, second cohort of 136 participants (Table 1). This cohort second cohort was deemed necessary in order to have sufficient statistical power to perform the desired association tests. Within the advanced-age, frail elderly cohort we performed logistic regression for each of the monocyte and DC markers in a univariate manner against the presence of chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease, asthma, dementia, cerebral vascular accident, diabetes mellitus, arrhythmia or anemia (Table 3). Other than a positive association between pDC frequency and dementia, no significant associations were observed for the frequencies of blood DCs. Although the senior and advanced-age, frail elderly groups had fewer monocytes expressing CCR2, there was no statistically significant association between monocyte CCR2 expression and disease (data not shown). In contrast, reductions in CX3CR1 expression only occurred in the advanced-age, frail elderly and individuals with elevated levels of CX3CR1 had a greater likelihood of having dementia, while reduced expression was associated with an increased risk of diabetes and anemia (Figure 3A). In addition there was a significant correlation between monocyte frequency and dementia, diabetes and anemia. The likelihood of having dementia was positively associated with monocytes and the classical to intermediate monocyte ratio, whereas for diabetes and anemia, opposite trends were observed (Figure 3B).


Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM - PLoS ONE (2014)

Representation of the differences in A) the expression of CX3CR1 on the classical (CLS), intermediate (INT) and non-classical (NON) monocyte subsets and B) the classical to intermediate monocyte ratio, between cases (grey) and controls (white) for dementia, diabetes mellitus and anemia.Comparison-wise p-value, **p<0.01, *p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126708&req=5

pone-0104522-g003: Representation of the differences in A) the expression of CX3CR1 on the classical (CLS), intermediate (INT) and non-classical (NON) monocyte subsets and B) the classical to intermediate monocyte ratio, between cases (grey) and controls (white) for dementia, diabetes mellitus and anemia.Comparison-wise p-value, **p<0.01, *p<0.05.
Mentions: To determine whether the observed alterations to monocyte and DC frequency and monocyte CCR2 and CX3CR1 expression in the advanced-age, frail elderly are associated with chronic disease, we analyzed a larger, second cohort of 136 participants (Table 1). This cohort second cohort was deemed necessary in order to have sufficient statistical power to perform the desired association tests. Within the advanced-age, frail elderly cohort we performed logistic regression for each of the monocyte and DC markers in a univariate manner against the presence of chronic obstructive pulmonary disease, congestive heart failure, coronary artery disease, asthma, dementia, cerebral vascular accident, diabetes mellitus, arrhythmia or anemia (Table 3). Other than a positive association between pDC frequency and dementia, no significant associations were observed for the frequencies of blood DCs. Although the senior and advanced-age, frail elderly groups had fewer monocytes expressing CCR2, there was no statistically significant association between monocyte CCR2 expression and disease (data not shown). In contrast, reductions in CX3CR1 expression only occurred in the advanced-age, frail elderly and individuals with elevated levels of CX3CR1 had a greater likelihood of having dementia, while reduced expression was associated with an increased risk of diabetes and anemia (Figure 3A). In addition there was a significant correlation between monocyte frequency and dementia, diabetes and anemia. The likelihood of having dementia was positively associated with monocytes and the classical to intermediate monocyte ratio, whereas for diabetes and anemia, opposite trends were observed (Figure 3B).

Bottom Line: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs).Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Whether these changes contribute to or are caused by these conditions warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT

Background: Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design: In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81-100 yrs), and compared against that of adults (19-59 yrs), and community-dwelling seniors (61-76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results: The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions: These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

Show MeSH
Related in: MedlinePlus