The effect of stress-inducible extracellular Hsp72 on human neutrophil chemotaxis: A role during acute intense exercise

Department of Physiology, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
Stress (Amsterdam, Netherlands) (Impact Factor: 2.72). 11/2008; 12(3):240-9. DOI: 10.1080/10253890802309853
Source: PubMed


We studied the physiological role of the 72 kDa extracellular heat shock protein (Hsp72, a stress-inducible protein) in modulating neutrophil chemotaxis during a single bout of intense exercise performed by sedentary women, together with various cell mechanisms potentially involved in the modulation. For each volunteer, we evaluated neutrophil chemotaxis and serum Hsp72 concentration before and immediately after a single bout of exercise (1 h on a cycle ergometer at 70% VO(2) max), and 24 h later. Both parameters were found to be stimulated by the exercise, and had returned to basal values 24 h later. In vitro, there was a dose-dependent increase in chemotaxis when neutrophils were incubated both with physiological Hsp72 concentrations and with a 100 x greater concentration. The chemotaxis was greater when the neutrophils were incubated with the post-exercise Hsp72 concentration than with the basal concentration, suggesting a physiological role for this protein in the context of the stimulation of neutrophil chemotaxis by intense exercise. The 100 x Hsp72 concentration stimulated chemotaxis even more strongly. In addition, Hsp72 was found to have chemoattractant and chemokinetic effects on the neutrophils at physiological concentrations, with these effects being significantly greater with the post-exercise than with the basal Hsp72 concentration. The Hsp72-induced stimulation of neutrophil chemotaxis disappeared when the toll-like receptor 2 (TLR-2) was blocked, and phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and nuclear transcription factor kappa B (NF-kappaB) were also found to be involved in the signaling process. No changes were observed, however, in neutrophil intracellular calcium levels in response to Hsp72. In conclusion, physiological concentrations of the stress protein Hsp72 stimulate human neutrophil chemotaxis through TLR-2 with its cofactor CD14, involving ERK, NF-kappaB, and PI3K, but not iCa(2 + ), as intracellular messengers. In addition, Hsp72 seems to participate in the stimulation of chemotaxis induced by a single bout of intense exercise performed by sedentary women.

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    • "eHSP70 function is, in general, associated with the activation of the immune system [21]. For example, eHSP70 has been reported to stimulate neutrophil microbicidal capacity [22] and chemotaxis [23] and recruitment of natural killer (NK) cells [24] as well as cytokine production by immune cells [12] [25]. In addition, eHSP70 was recently hypothesized to be involved in the inducement of neural cell protection under stress conditions [15]. "
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    ABSTRACT: Recent evidence shows divergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For example, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways. Increased eHSP70 is associated with inflammatory and oxidative stress conditions, whereas decreased iHSP70 levels are related to insulin resistance in skeletal muscle. Serum eHSP70 concentrations are positively correlated with markers of inflammation, such as C-reactive protein, monocyte count, and TNF-α, while strategies to enhance iHSP70 (e.g., heat treatment, chemical HSP70 inducers or coinducers, and physical exercise) are capable of reducing the inflammatory profile and the insulin resistance state. Here, we present recent findings suggesting that imbalances in the HSP70 status, described by the [eHSP70]/[iHSP70] ratio, may be determinant to trigger a chronic proinflammatory state that leads to insulin resistance and T2DM development. This led us to hypothesize that changes in this ratio value could be used as a biomarker for the management of the inflammatory response in insulin resistance and diabetes.
    Mediators of Inflammation 02/2015; 2015. DOI:10.1155/2015/249205 · 3.24 Impact Factor
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    • "Moreover, by using flow cytometry, we demonstrated that HspA1A bound to TLR2 and TLR4 was expressed on neutrophils. Our data are in agreement with several reports showing that extracellular HspA1A serves as a ligand for TLRs (Asea 2008; Giraldo et al. 2010; Ortega et al. 2009). Others have also documented the ability of extracellular HspA1A to stimulate neutrophil phagocytic function via TLR2 (Giraldo et al. 2010), as well as to induce IL-8 and TNF-α production via TLR4 (Wheeler et al. 2009) and to induce production of pro-inflammatory cytokines via TLR2 and TLR4 (Asea et al. 2002). "
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    ABSTRACT: Inducible heat shock protein (HspA1A) promotes tumor cell growth and survival. It also interacts with effector cells of the innate immune system and affects their activity. Recently, we showed that the direct contact of ovarian cancer cells, isolated from tumor specimens, with neutrophils intensified their biological functions. Our current experiments demonstrate that the activation of neutrophils, followed by an increased production of reactive oxygen species, by cancer cells involves the interaction of HspA1A from cancer cells with Toll-like receptors 2 and 4 expressed on the neutrophils' surface. Our data may have a practical implication for targeted anticancer therapies based, among other factors, on the inhibition of HspA1A expression in the cancer cells.
    Cell Stress and Chaperones 04/2012; 17(6):661-74. DOI:10.1007/s12192-012-0338-2 · 3.16 Impact Factor
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    • "The eHSP72 function is in general associated with the activation of the immune system (Whitham and Fortes 2008). For example, eHSP72 has been reported as an inductor of neutrophils microbicidal capacity (Ortega et al. 2006) and chemotaxis (Ortega et al. 2009), recruitment of NK (natural killer) cells (Horn et al. 2007) as well as cytokine production in immune cells (Asea et al. 2000; Johnson and Fleshner 2006). Besides that, eHSP72 was recently shown to be involved in the inducement of neural cell protection under stress conditions (Krause and Rodrigues-Krause Jda 2011). "
    Cell Stress and Chaperones 01/2012; 17(3):293-302. DOI:10.1007/s12192-011-0319-x · 3.16 Impact Factor
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