Elsevier

Life Sciences

Volume 75, Issue 11, 30 July 2004, Pages 1357-1368
Life Sciences

Stress and immunological phagocytosis: possible nongenomic action of corticosterone

https://doi.org/10.1016/j.lfs.2004.02.026Get rights and content

Abstract

Some immunological responses triggered by stress can be mediated by corticosterone activity through cytosolic receptors regulating gene expression. There are, however some reports on the possibility of a nongenomic effect of this hormone to explain phenomena observed in a few minutes. We have found that macrophages from mice subjected to 10 min of cold stress (at −15 °C) showed a lower phagocytic capacity mediated by Fcγ-receptors than cells from control animals. Treating mice with glucocorticoid antagonist RU 486 did not block the decrease in phagocytic capacity. This inhibitory effect on phagocytosis was also observed by experiments in vitro with corticosterone in the concentration found in serum after stress, and could not be prevented by RU 486, actinomicyn D or cycloheximide. These results indicate that corticosterone could affect phagocytosis by macrophages through a nongenomic mechanism, and may have physiological implications.

Introduction

When homeostasis is threatened  a physiological condition generally known as stress (Selye, 1950)  a complex adaptative response develops, which in mammalian organisms may involve the central nervous system, the hypothalamic-pituitary-adrenal (HPA) axis and the peripheral autonomic nervous system (Stratakis and Chrousos, 1995). Signals in the hypothalamus induce the release of corticotropin releasing hormone (CRH) into the hypophyseal portal system and this hormone stimulates the pituitary corticotropin (ACTH) secretion. Circulating ACTH stimulates the adrenal to secrete glucocorticoids, which are one of the main effector molecules following the activation of the HPA axis Sternberg et al., 1992, Stratakis and Chrousos, 1995. These hormones have been shown to produce effects on immune response axis Sternberg et al., 1992, Besedovsky and Del Rey, 1996, Stratakis and Chrousos, 1995, Dhabhar, 2002. They can inhibit antigen presentation and the expression of the major histocompatibility complex class II proteins (MHCII), reduce activation and proliferation of T and B cell, the accumulation of phagocytes at inflammatory sites and affect the phagocytosis Snyder and Unanue, 1982, Cronstein et al., 1992, Dhabhar et al., 1996, Ashwell et al., 2000.

The endogenous glucocorticoids, corticosterone and cortisol, are the most studied substances involved in stress responses. These hormones have very different actions on many kinds of cells. In the classical model of glucocorticoid action, the hormone freely diffuses across plasma membranes and bind to cytosolic receptors in target cells. This complex moves into the nucleus, where it binds in specifics DNA sequences, called hormone response elements and regulates the expression of some gene Yamamoto, 1985, Marx, 1995.

This traditional genomic theory of steroid action does not fully explain the rapid effects of glucocorticoid hormones. Numerous reports described rapid and nongenomic effects of steroid hormones Liu et al., 1995, Qiu et al., 1998, Lou and Chen, 1998, Chen and Qiu, 1999, Li et al., 2001, Qiu et al., 2001, Park et al., 2001, Han et al., 2002. In these articles the authors use transcription and translation inhibitors to show that the glucocorticoids actions do not depend of expression of new proteins. Some authors propose the existence of membrane receptors that could activate protein kinases, open ion channels, change the phospholipid turnover and increase cAMP and calcium intracellular levels (Chen and Qiu, 1999).

Most studies about nongenomic actions of glucocorticoids have been realized in isolated systems or cultured cells. However it is probable that in the organisms these nongenomic responses could also be observed, since the concentrations of glucocorticoid used in some of these experiments are in the physiological range.

In this article, we investigate the rapid effect of cold stress on immunological phagocytosis mediated by the Fcγ receptors by mice peritoneal macrophages and propose that this effect could be caused by corticosterone through nongenomic action.

Section snippets

Reagents and media

Phosphate buffered saline (PBS) containing 0.9% NaCl and 0.007 M phosphate buffer, pH 7.2 was used. Hanks' medium was prepared as described in Paul (1970). RPMI-1640 tissue culture medium with L-glutamine and 25 mM HEPES, penicillin, streptomycin sulfate, corticosterone, actinomycin D, cycloheximide and mifepristone were obtained from Sigma Chemical Co (St. Louis, MO, USA); fetal calf serum from Life Technologies (New York, NY, USA); dimethyl sulfoxide (DMSO) from Merck (Darmstadt, Germany).

Animals and cells

Ten minutes of cold stress promote decrease in Fcγ-receptor mediated phagocytosis and this effect is not inhibited by treatment of mice with glucocorticoid receptor antagonist RU 486

The experiments in Fig. 1A show the effects of cold stress on the phagocytosis of IgG opsonized red cells. It is shown that macrophages from mice which were subjected to 10 min of stress at −15 °C, had a lower capacity to phagocytize this type of immune complex than the cells from control animals, kept at room temperature (25 °C). Phagocytosis experiments were performed in vitro with the cells at 37 °C. In these experiments 90 percent of cells were macrophages and apparently the cold stress did

Discussion

We have found that when mice were subjected to a rapid cold stress (10 min. at −15 °C) their peritoneal macrophages showed a decrease in phagocytosis mediated by Fcγ receptors, without affecting the capacity for interaction as measured by rosettes formation. This short stress condition produced a great increase in serum corticosterone concentration, and additional experiments in vitro demonstrated that this hormone could induce the observed decrease in phagocytic capacity of these cells. There

Acknowledgements

We thank: Dr. José A. Rodrigues and Dr. Margaret de Castro for their help in the determination of corticosterone concentration, Dr. Vitor D. Galban for valuable assistance with graphic computation, Silvana C. Silva and José A. da Silva for technical assistance and Maria Thereza Rodrigues for typing the manuscript. This investigation was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo and FAEPA.

References (47)

  • S.H. Peers et al.

    Reversal of the anti-inflammatory effects of dexamethasone by the glucocorticoid antagonist RU 38486

    Biochem. Pharmacol.

    (1988)
  • J. Qiu et al.

    Rapid activation of ERK1/2 mitogen-activated protein kinase by corticosterone in PC12 cells

    Biochem. Biophys. Res. Commun.

    (2001)
  • J. Qiu et al.

    Nongenomic mechanism of glucocorticoid inhibition of bradykinin-induced calcium influx in PC12 cells: possible involvement of protein kinase C

    Life Sciences

    (2003)
  • A.G. Reddy et al.

    Effect of estradiol on the membrane fluidity of the rat vaginal epithelial cells

    J. Steroid. Biochem.

    (1989)
  • W. Rong et al.

    Rapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats

    Brain Res.

    (1999)
  • S. Shivaji et al.

    Steroid-induced perturbations of membranes and its relevance to sperm acrosome reaction

    Biochim. et Biophys. Acta

    (1992)
  • B.G. Zhu et al.

    Rapid enhancement of high affinity glutamate uptake by glucocorticoids in rat cerebral cortex synaptosomes and human neuroblastoma clone SK-N-SH: possible involviment of G-protein

    Biochem. Biophys. Res. Commun.

    (1998)
  • J.D. Ashwell et al.

    Glucocorticoids in T Cell Development and Function

    Annu. Rev. Immunol.

    (2000)
  • T. Bengtsson et al.

    Actin dynamic in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium

    Eur. J. Cell Biol.

    (1993)
  • H.O. Besedovsky et al.

    Immune-endocrine interactions: Facts and hyphotheses

    Endocr. Rev.

    (1996)
  • R. Clarke et al.

    Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17β-estradiol

    J. Natl. Cancer Inst.

    (1990)
  • B.N. Cronstein et al.

    A mechanism for the antiinflamatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1

    Proc. Natl. Acad. Sci. USA

    (1992)
  • F.S. Dhabhar et al.

    Stress-Induced Changes in Blood Leukocyte Distribution—Role of Adrenal Steroid Hormones

    J Immunol.

    (1996)
  • Cited by (0)

    View full text