Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen

Engler, Harald; Bailey, Michael T.; Engler, Andrea; Sheridan, John F.

doi:10.1016/j.jneuroim.2003.11.011

Cited by 177 publications

(180 citation statements)

References 47 publications

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“…Exposure of mice to CS for 3 days resulted in accumulation of all three major stages of granulocyte development in the bone marrow (increases of 100%, 40%, and 42% in mature, intermediate, and immature granulocytes, respectively; Table 2). This is in keeping with the observations that the addition of small amounts of Gc to bone marrow cultures promoted an accumulation of myeloid cells and gradual loss of lymphoid cells (23), with similar accumulations, including immature granulocytes, observed in vivo in mice responding to social stress (21). Thus, the findings here expand on these earlier studies.…”

Section: Discussionsupporting

confidence: 91%

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Trottier

Newsted

King

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Natural glucocorticoids (Gc) produced during stress have profound effects on the immune system. It is well known that Gc induce apoptosis in precursor T and B cells, markedly altering lymphopoiesis. However, it has been noted that marrow myeloid cells expanded both in proportion and absolute numbers in the mouse after Gc exposure. Mice were implanted with a corticosterone (CS) tablet that increased serum Gc and caused atrophied thymuses, both classic signs of activation of the stress axis. Blood neutrophil counts were elevated (4.8؋), whereas lymphocyte counts declined. Flow cytometric analysis of the marrow revealed that the phenotypic distribution of the various major classes of cells was shifted by Gc exposure. As expected, marrow lymphocyte numbers declined >40% after 3 days of exposure to Gc. Conversely, in the myeloid compartment, both monocytes and granulocytes increased in number by >40%. Further, all granulocyte developmental stages showed large increases in both total number and percentage of cells. To investigate the functional capacity of mature granulocytes from Gc-treated mice, an improved granulocyte isolation method was developed. Gc exposure had little effect on the ability of granulocytes to produce superoxide or undergo chemotaxis or phagocytose bacteria. These results indicate that Gc treatment shifts bone marrow composition and provides evidence that granulocytes and their progenitors are selectively preserved under stressful conditions without losing function.granulopoiesis ͉ lymphopoiesis

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Section: Discussionsupporting

confidence: 91%

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Trottier

Newsted

King

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…IL-1β stimulates the expression and secretion of myelopoietic cytokines (e.g., colony-stimulating factors) in stromal cells of the bone marrow and modulates the expression of adhesion molecules, resulting in the accelerated release of myeloid cells from the marrow and their migration to lymphoid tissues (Dinarello, 1996). We have previously demonstrated that SDR was associated with an increase in the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bone marrow, enhanced myelopoiesis, and a massive accumulation of CD11b + cells in the blood and the spleen (Engler et al, 2004(Engler et al, , 2005. Since IL-1R1 −/− mice subjected to the stressor did not show enhanced myelopoiesis in the bone marrow nor substantial increases of CD11b + cell numbers in the blood and the spleen, we conclude that IL-1 was mediating the stress-associated mobilization and redistribution of GC-insensitive cells to the spleen which ultimately resulted in a decreased GC sensitivity of this tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the socially defeated mice were also more susceptible to endotoxic shock and, after in vivo challenge with LPS, showed significantly higher IL-1β and TNF-α expression in the spleen (Quan et al, 2001). The stressassociated decrease in the GC sensitivity of LPS-stimulated splenocytes was dependent on the presence of GC-insensitive CD11b + myeloid cells, which have been shown to be mobilized from the bone marrow (Engler et al, 2004(Engler et al, , 2005. Removal of these cells prior to cell culture abolished the stressor-induced effects on both cell survival and cytokine production .…”

Section: Introductionmentioning

confidence: 94%

Interleukin-1 receptor type 1-deficient mice fail to develop social stress-associated glucocorticoid resistance in the spleen

Engler

Bailey

Engler

et al. 2008

Psychoneuroendocrinology

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SummaryFrequent or chronic stress as a result of repeated or persistent exposure to social challenges has been shown to affect the glucocorticoid (GC) responsiveness of immune cells in mice. Lipopolysaccharide-stimulated splenocytes of mice that were repeatedly subjected to social disruption were less sensitive to the anti-inflammatory actions of GC as evident from an increased production of pro-inflammatory cytokines and enhanced cell survival. The development of functional GC resistance was accompanied by the accumulation of GC-insensitive CD11b + cells in the spleen. These cells were shown to exhibit impaired nuclear translocation of the GC receptor and lack of GCinduced suppression of NF-κB. Similar impairments in GC receptor function have been reported after in vitro treatment of various cell lines with interleukin (IL)-1. The aim of this study was to elucidate whether IL-1 is a critical factor for the development of GC resistance in socially stressed mice. In the first experiment, we investigated if repeated social stress alters plasma levels and tissue gene expression of IL-1α and IL-1β. It revealed that recurrent stressor exposure significantly increased splenic and hepatic mRNA expression and the plasma protein level of IL-1β, and hepatic mRNA expression of IL-1α. In the second experiment, IL-1 receptor type 1 (IL1R1)-deficient mice were subjected to the stressor and both the tissue distribution of CD11b + cells and the GC sensitivity of the splenocytes were compared to wildtype mice. Mice lacking the IL1R1 exhibited adrenal hypertrophy, thymic involution, and elevated serum corticosterone levels in response to the stressor but did not show splenic accumulation of CD11b + cells and failed to develop GC resistance. These findings suggest that IL-1 plays a critical role in the development of the social stress-associated GC resistance in the murine spleen.

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“…Одновре-менно авторами наблюдалось нарушение про-лиферативной активности лимфоцитов (задолго до экзаменов), при этом подчеркивается, что сразу после воздействия стрессора число цито-токсических Т-клеток и натуральных киллеров возрастает благодаря мобилизации пула из депо, а их пролиферативная активность в ответ на ми-тоген падает. Фагоцитарная активность макро-фагов возрастала, однако острый стресс снижал чувствительность данных клеток к повторному воздействию стрессовых гормонов [5,8,11,12]. Перечисленные реакции системы иммунитета коррелировали с выраженностью реакций кар-диоваскулярной системы: повышение частоты сердечных сокращений, уровней систолическо-го и диастолического артериального давления, уменьшение величины кардиоинтервала [7,9].…”

Section: результаты и обсуждениеunclassified

“…В качестве адаптив-ной реакции на стресс происходит активация хе-мотаксиса, адгезивной способности лейкоцитов, рост их миграционной активности. Более того, психоэмоцональный стресс приводит к перерас-пределению клеток и на уровне костного моз-га -происходит стимуляция миелопоэза, акку-муляция нейтрофилов и лимфоцитов в селезенке [2,8,13,14]. Такие эффекты реализуются благо-даря четкому медиаторному нейроиммуноэндо-кринному контролю сложных ответных реакций на психоэмоциональный стресс.…”

Section: результаты и обсуждениеunclassified

Features of Immune Reactions in Stress Conditions Associated Associated With Exams

Широлапов¹,

Пятин²,

Лавров³

2014

Med. immunol.

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ОсОбеннОсти иммунОлОгических пОказателей в услОвиях экзаменациОннОгО стрессаШиролапов И.В., Пятин В.Ф., Лавров О.В. ГОУ ВПО «Самарский государственный медицинский университет» Минздравсоцразвития России, г. СамараРезюме. В условиях воздействия психоэмоциональных стрессоров обеспечивается постоянное тесное взаимодействие нервной, эндокринной и иммунной физиологических регуляторных систем. У 203 студентов вуза изучены особенности клеточных и гуморальных показателей системы имму-нитета при экзаменационном стрессе. Установлено снижение абсолютного и относительного со-держания CD3 + Т-лимфоцитов, субпопуляции клеток с функцией естественной цитотоксичности (CD3 -CD16 + CD56 + и CD3 + CD16 + CD56 + клеток) после экзамена по сравнению с таковым до экзаме-на. Выявлено снижение значений CD3 -CD19 + , CD3 + CD4 + и CD3 + CD8 + лимфоцитов после экзамена относительно контрольного периода измерений. Сывороточные концентрации иммуноглобулинов A, M, G находились в пределах физиологических значений нормы. Изменения иммунологических показателей при остром экзаменационном стрессе зависят от особенностей вегетативных и гормо-нальных реакций человека и в определенных условиях -предельных по интенсивности и длительно-сти -психоэмоциональный стресс может вызвать общие нарушения иммунного реагирования. It has been widely accepted that routine psychophysiological stressors may influence immune functioning via their close interactions between nervous, autonomic, endocrine and immune regulatory systems. The aim of this study was to evaluate immune reactions to acute psychophysiological stress in 203 medical students before and after academic exams. The results showed significant decrease of absolute and relative contents CD3 + T cells, natural killer (NK) cell subpopulations and T-NK cells (CD3 -CD16 + CD56 + and CD3 + CD16 + CD56 + ), as well as declined NK cell activity were revealed immediately after exams, as compared to initial values for these indices. Moreover, a significant decrease in CD19 + B cells, CD4 + T-helpers and CD8 + T-cytotoxic lymphocyte counts was found after exams, in comparison with parameters assessed under stress-free conditions, but no differences were observed, when compared with pre-examination values. Serum concentrations of IgA, IgM, IgG were within normal physiological limits. Changes in immunological parameters during acute examination-associated stress depend on characteristics of autonomous and hormonal reactions in humans, and, under particular extreme conditions, such psycho-emotional stress may cause general disturbances of immune reactions. We conclude that acute psycho-physiological stress during the exams causes significant changes in some lymphocyte subpopulations, in particular, natural killers.

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Effects of repeated social stress on leukocyte distribution in bone marrow, peripheral blood and spleen

Cited by 177 publications

References 47 publications

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Interleukin-1 receptor type 1-deficient mice fail to develop social stress-associated glucocorticoid resistance in the spleen

Features of Immune Reactions in Stress Conditions Associated Associated With Exams

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