Heat Shock Protein 32 in Human Peripheral Blood Mononuclear Cells: Effect of Aging and Inflammation

Geriatric Unit, Academic Hospital, Vrije Universiteit Brussel, Belgium.
Journal of Clinical Immunology (Impact Factor: 3.18). 10/2005; 25(5):405-17. DOI: 10.1007/s10875-005-5361-y
Source: PubMed


The purpose of the present study was to assess the influence of age and acute infection on the production of Hsp32 in human peripheral blood cells, using flow cytometry. Thirty-five controls and 31 patients with acute infection participated. We found that the age and inflammatory status correlated positively with Hsp32 levels in both heat shocked (HS) and non-HS monocytes and lymphocytes. In addition, the HS response of Hsp32 was different in these peripheral blood cells; whereas HS exerted an up-regulation in the levels of Hsp32 in monocytes, a significant decrease in Hsp32 levels was noticed for lymphocytes. We found significant relationships between circulating C-reactive protein as well as interleukin-6 and the levels of Hsp32 in cells. We conclude that Hsp32 is up-regulated in the elderly as well as in individuals with inflammation, and that the HS response of Hsp32 is different in monocytes as compared to lymphocytes.

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    • "Notably, under normal physiological situations, oxidative damage to cells can result from reaction with oxygen radicals formed as a by-product of normal metabolism (Wheeler et al., 1995). Such damages, as has been demonstrated by various studies (Arata et al., 1995; Bechoua et al., 1999; Njemini et al., 2005), can result in the induction of the HSP gene family which protects proteins from denaturation. Accordingly, the limited availability of glutathione in CD4 + cells may lead to enhanced Hsp70 expression as a result of the potential accumulation of reactive oxygen metabolites (Schreck et al., 1991; Lautier et al., 1992; Chang et al., 1999). "
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    ABSTRACT: Cell stress responses are ubiquitous in all organisms and are characterized by the induced synthesis of heat shock proteins (Hsp). Previous studies as well as recent reports by our group have consistently suggested that aging leads to an increase in the basal levels of Hsp70. Here we extend these studies by examining the differential Hsp70 response of peripheral blood lymphocyte (PBL) subsets. It is well established that with aging, one of the major changes in the T cell pool is an expansion of T cells with the memory phenotype as well as those deficient for the CD28 molecule. To determine if alterations in the frequency of T cell subsets might be responsible for the observations, we have carried out a more comprehensive flow cytometric analysis of the various phenotypes of PBL under unstimulated conditions. Cells were obtained from 10 young and 10 elderly normal subjects. The basal Hsp70 levels in the various PBL phenotypes were comparable between young and elderly subjects. However, different patterns of Hsp70 response were noticed among the PBL subtypes, which were similar in both young and elderly subjects. In particular, the memory cell phenotypes produced more Hsp70 than the naïve phenotypes. These results suggest that aging-related changes in basal Hsp70 levels in PBL are linked to the altered frequency of lymphocyte subsets and not to increases in aged lymphocytes per se. In addition, the increase in Hsp70 can be interpreted as the result of a tendency towards more pronounced cellular differentiation in aging.
    Aging cell 07/2008; 7(4):498-505. DOI:10.1111/j.1474-9726.2008.00401.x · 6.34 Impact Factor
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    • "Overall, immunosenescence is associated with a general decline in macrophage function (Sebastian et al 2005), possibly due to impaired ability of macrophages to respond to activation or due to a decline in activation signals from other cells. The antigen-presenting capacities of peripheral blood monocytes from older humans appears to be compromised due to alterations in MHC class II gene expression (Villanueva et al 1990), and the activities of infection-response proteins, such as heat shock proteins, may also be altered (Njemini et al 2005). In one human study that did obtain macrophages directly from the lungs, investigators found a decrease in accessory function of these cells (Zissel et al 1999). "
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    ABSTRACT: Aging is associated with a dysregulation of the immune system known as immunosenescence. Immunosenescence involves cellular and molecular alterations that impact both innate and adaptive immunity, leading to increased incidences of infectious disease morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. While current data suggests physical activity may be an effective and logistically easy strategy for counteracting immunosenescence, it is currently underutilized in clinical settings. Long-term, moderate physical activity interventions in geriatric populations appear to be associated with several benefits including reduction in infectious disease risk, increased rates of vaccine efficacy, and improvements in both physical and psychosocial aspects of daily living. Exercise may also represent a viable therapy in patients for whom pharmacological treatment is unavailable, ineffective, or inappropriate. The effects of exercise impact multiple aspects of immune response including T cell phenotype and proliferation, antibody response to vaccination, and cytokine production. However, an underlying mechanism by which exercise affects numerous cell types and responses remains to be identified. Given this evidence, an increase in the use of physical activity programs by the healthcare community may result in improved health of geriatric populations.
    Clinical Interventions in Aging 02/2007; 2(1):3-16. DOI:10.2147/ciia.2007.2.1.3 · 2.08 Impact Factor
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    ABSTRACT: The present review of published data and the authors’ own results addresses the role of heat shock proteins in the regulation of cell and tissue homeostasis and considers the decrease in their expression levels as one of the main factors of aging. Heat shock proteins are involved in the regulation of proliferation, apoptosis, and differentiation of cells, as well as in that of intracellular homeostasis, and, therefore, play a substantial role in maintaining the activity of the immune, cardiovascular, and other systems of the organism. These proteins are also implied in the development of atherosclerosis, myocardial infarction, ischemic stroke, and other diseases accompanied by thrombotic complications. The use of short peptides provides an opportunity to restore and normalize the expression of heat shock proteins, which probably accounts for the antistress and geroprotective activity of these peptides.
    07/2012; 2(3). DOI:10.1134/S2079057012030071
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