Sleep and circadian rhythm regulate circulating complement factors and immunoregulatory properties of C5a

Reis, Edimara S.; Lange, Tanja; Köhl, Gabriele; Herrmann, Anne; Tschulakow, Alexander; Naujoks, Julius; Born, Jan; Köhl, Jörg

doi:10.1016/j.bbi.2011.04.011

Cited by 68 publications

(78 citation statements)

References 50 publications

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“…This is a very intriguing study because it confirms our recently published data that adult ADHD is associated with alterations in circadian rhythm at behavioral and endocrine molecular levels (Baird, Coogan, Siddiqui, Donev, & Thome, 2011). Furthermore, a recent study showed that sleep and circadian rhythm regulate circulating immunoregulatory properties of C5a anaphylatoxin, a product of complement activation (Reis et al, 2011). This study found that C5a concentration in blood is low in the evenings, increases during sleep, and reaches a maximum in mornings.…”

Section: Polymorphisms In Adhdsupporting

confidence: 82%

Polymorphisms in Neuropsychiatric and Neuroinflammatory Disorders and the Role of Next Generation Sequencing in Early Diagnosis and Treatment

Donev

Howell

2012

Challenges and Opportunities of Next-Generation Sequencing for Biomedical Research

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Section: Polymorphisms In Adhdsupporting

confidence: 82%

Polymorphisms in Neuropsychiatric and Neuroinflammatory Disorders and the Role of Next Generation Sequencing in Early Diagnosis and Treatment

Donev

Howell

2012

Challenges and Opportunities of Next-Generation Sequencing for Biomedical Research

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“…When comparing our study design to common sleep deprivation studies, in which significant immunological impacts were reported [12,51,52], one can notice four major differences that may account for the apparent incongruence in results. In our study we: (i) measured in vivo plasma cytokine levels, as opposed to assessing in vitro ‘induced production' levels; (ii) allowed participants to maintain normal daily routine following baseline assessment and up until the beginning of the sleep deprivation period, rather than restricting them to the laboratory; (iii) added social and physiological activities during the sleep deprivation period, as opposed to keeping participants under conditions of social isolation and minimal physical activity during the sleep deprivation period, and (iv) assessed immune indices following completion of the entire paradigm, when participants were ready to resume their daily activity rather than assessing immunity at specific time points along the night period and in close conjunction with the potentially acute stress responses.…”

Section: Discussionmentioning

confidence: 99%

Resilience of the Immune System in Healthy Young Students to 30-Hour Sleep Deprivation with Psychological Stress

Matzner¹,

Hazut²,

Naim³

et al. 2013

Neuroimmunomodulation

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Objective: Young adults often encounter sleep deprivation and stressful events. Both have been separately reported to modulate immunity, and occasionally they occur simultaneously. We assessed the combined effects of these conditions on immune competence in healthy students. Methods: Twenty-three participants (mean age 24 years; SD 1.86; 14 females) were exposed to 30 h of sleep deprivation during which they conducted physiological, social and cognitive tasks. The control group consisted of 18 participants (mean age 23.67 years; SD 1.46; 11 females). All participants underwent cognitive and psychological evaluations at 10:00 AM, followed by blood and saliva collection, 3 days before sleep deprivation induction and on the morning following it. Immune/endocrine measures included blood counts of lymphocytes, granulocytes, monocytes and natural killer (NK) cells; levels of several cell surface markers; NK cytotoxicity; plasma levels of interleukin (IL)-6, IL-10, dehydroepiandrosterone and neuropeptide Y, and plasma and salivary cortisol levels. Results: Although the experimental protocol significantly elevated state anxiety and psychological dissociation levels, no effects were evident in any of the immunological/endocrine indices. In contrast, expected sex differences in immune measures were found, including significantly higher NK cytotoxicity and monocyte counts in males, validating the integrity of the measurements. Conclusions: The findings suggest resilience of the immune system to a combined sleep deprivation and stressful exposure in young adults, while previous studies reported immune perturbations following either of these conditions separately. These apparent contradictions might reflect differences in the study design or in the methodology used for immunological assessments, including the time of sample collection, the combination of sleep deprivation with stress and our in vivo assessment of cytokine levels.

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“…All of these cascades also show circadian rhythms in activation due to a drop in blood pH during deep sleep at night and are most likely responsible for circadian changes in HSPC trafficking in PB. 23,24 Therefore, in addition to circadian changes in the tonus of the vegetative nervous system, circadian activation of the ComC, CoaC, and FibC is most likely also involved in the circadian release of HSPCs from BM into PB. 25 What is also important, the three cascades show a vigorous crosstalk due to mutual cross-activation by proteolytic enzymes released, for example, during inflammation.…”

Section: Discussionmentioning

confidence: 99%

Novel evidence that crosstalk between the complement, coagulation and fibrinolysis proteolytic cascades is involved in mobilization of hematopoietic stem/progenitor cells (HSPCs)

et al. 2014

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The role of blood proteinases in the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not well understood. As previously reported, activation of the complement cascade (ComC) and cleavage of C5 by C5 convertase are enabling events in the release of C5a that plays a crucial role in the egress of HSPCs from bone marrow (BM) into peripheral blood (PB) and explains why C5-deficient mice are poor mobilizers. Here we provide evidence that during granulocyte colony-stimulating factor- and AMD3100-induced mobilization, not only the ComC but also two other evolutionarily ancient proteolytic enzyme cascades, the coagulation cascade (CoaC) and the fibrynolytic cascade (FibC), become activated. Activation of all three cascades was measured by generation of C5a, decrease in prothrombin time and activated partial thromboplastin time as well as an increase in the concentrations of plasmin/antiplasmin and thrombin/antithrombin. More importantly, the CoaC and FibC, by generating thrombin and plasmin, respectively, provide C5 convertase activity, explaining why mobilization of HSPCs in C3-deficient mice, which do not generate ComC-generated C5a convertase, is not impaired. Our observations shed more light on how the CoaC and FibC modulate stem cell mobilization and may lead to the development of more efficient mobilization strategies in poor mobilizers. Furthermore, as it is known that all these cascades are activated in all the situations in which HSPCs are mobilized from BM into PB (for example, infections, tissue/organ damage or strenuous exercise) and show a circadian rhythm of activation, they must be involved in both stress-induced and circadian changes in HSPC trafficking in PB.

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Sleep and circadian rhythm regulate circulating complement factors and immunoregulatory properties of C5a

Cited by 68 publications

References 50 publications

Polymorphisms in Neuropsychiatric and Neuroinflammatory Disorders and the Role of Next Generation Sequencing in Early Diagnosis and Treatment

Polymorphisms in Neuropsychiatric and Neuroinflammatory Disorders and the Role of Next Generation Sequencing in Early Diagnosis and Treatment

Resilience of the Immune System in Healthy Young Students to 30-Hour Sleep Deprivation with Psychological Stress

Novel evidence that crosstalk between the complement, coagulation and fibrinolysis proteolytic cascades is involved in mobilization of hematopoietic stem/progenitor cells (HSPCs)

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