The experimental data reviewed herein is aimed at an evaluation of the circadian dynamics of neutrophil phagocytosis (basal phagocytosis, phagocytic response, and adherence) in mice and rats and attempts to establish whether the functional pinealectomy accomplished through constant light exposure affects the level and/or circadian oscillation of the parameters. In both species, basal phagocytic activity appears as a periodic function, peaking in the second half of the night (03:00- 04:00). Adherence to nylon fibres displays a circadian oscillation with two maxima (10:00 and 22:00). Under constant light, the mean phagocytic activity is lowered by 40%, but its circadian amplitude increases, while the acrophase occurs earlier. Both the mean adherence level and its circadian variation are depressed, the latter to a larger extent. The amplitude and shape of the phagocytic response in non-immunised mice appears to depend on the time of the day when antigenic stimulation occurs, thus on the phase of the basal rhythm, drawing attention to the necessity for careful circadian scheduling of immunomodulatory interventions. The results suggest that rhythmic phagocytosis is part of the immune system's circadian oscillation, controlled by hypothalamic centres and susceptible to modulation under the impact of endogenous and exogenous factors, including melatonin and the light-dark cycle.
phagocytosis; neutrophils; circadian rhythms; light; melatonin; hypothalamus
Abe M, Herzog ED, Yamazaki S, Straume M, Tei H, Sakaki Y, Menaker M, Block GD: Circadian rhythms in isolated brain regions. J Neurosci 22:350-356, 2002.
Akbulut H, Icli F, Buyukcelik A, Akbulut KG, Demirci S: The role of granulocyte-macrophage-colony stimulating factor, cortisol, and melatonin in the regulation of the circadian rhythms of peripheral blood cells in healthy volunteers and patients with breast cancer. J Pineal Res 26:1-8, 1999.
Angeli A, Gatti G, Sartori ML, Del Ponte D, Cerignola R: Effects of exogenous melatonin on human natural killer (NK) cells activity. An approach to the immunomodulatory role of the pineal gland. In Gupta D, Attanasio A, Reiter RJ (eds.): The pineal gland and cancer. 1988, pp. 145-147.
Arendt J: Melatonin and the Mammalian Pineal Gland. Chapman and Hall, London, 1995.
Arendt J: Role of the pineal gland and melatonin in seasonal reproductive function in mammals. Oxford Reviews of Reproductive Biology 8:266-320, 1986.
Arias J, Melean E, Valero N, Pons H, Chacin-Bonilla L, Larreal Y, Bonilla E: Effect of melatonin on lymphocyte proliferation and production of interleukin-2 (IL-2) and interleukin-1 beta (IL-1 beta) in mice splenocytes (In Spanish). Invest Clin 44:41-50, 2003.
Baciu I, Benetato G, Secareanu S: L'influence des fractions globuliniques du serum, isolees par chromatographie sur colonne a derives cellulosiques, sur la phagocytose. 5eme Congres Mondial de Biochimie, Moscou, 1961.
Baciu I, Olteanu A, Prodan T, Baiescu M, Vaida A: Changes of phagocytic biological rhythm by reduction of circadian times and by influences upon hypothalamus. Int J Neurosci 41:143-153, 1988.
Baciu I, Cornelissen C, Olteanu A, Halberg F: Chrono-meta-analysis of circadian phagocytosis rhythms in blood of ginea pigs on two different lighting regimens. Chronobiologia 21:299-302, 1994.
Baciu I, Felegean A, Maghiar T, Hozan C, Albu M: Effects of thymectomy on blood neutrophils phagocytic activity and phagocytic response in mice. Rom J Physiol 33:75-81, 1996.
Baciu I, Hriscu M, Saulea G: Hypothalamic mechanisms of immunity. Intern J Neurosci 113:259-277, 2003.
Barjavel MJ, Mamdouh Z, Raghbate N, Bakouche O: Differential expression of the melatonin receptor in human monocytes. J Immunol 160:1191-1197, 1988.
Barriga C, Martin MI, Tabla R, Ortega E, Rodriguez AB: Circadian rhythm of melatonin corticosterone and phagocytosis: effect of stress. J Pineal Res 30:180-187, 2001.
Belluardo N, Mudo G, Bindoni M: Effects of early destruction of the mouse arcuate nucleus by monosodium glutamate on age-dependent natural killer activity. Brain Res 534:225-233, 1990.
Benetato G, Baciu I, Vlad L: Zentralnerven-system und Abwehrfunction. Die Rolle der hypothalamischen vegetativen Zentren bei der Phagozytentatigkeit Schweiz Med Wochenschr 75:702-712, 1945.
Benetato G, Oprisiu C, Baciu I: Systeme nerveux central et phagocytose (contributions experimentales grace a la methode de la "tete isolee"). J Physiol 39:191-197, 1947.
Berger J: Changes in marrow myelopoietic and lymphoid cell counts after repeated cyclophosphamide administration in rats. Haematologia 14:407-416, 1981.
Berger J, Slapnickova M: Circadian structure of rat neutrophil phagocytosis. Comp Clin Path 12:84-89, 2003.
Berk ML, Finkelstein JA: An autoradiographic determination of the efferent projections of the suprachiasmatic nucleus of the hypothalamus. Brain Res 226:1-13, 1981.
Bongrand P, Bouvenot G, Bartolin R, Tatossian J, Bruguerolle B: Are there circadian variations of polymorphonuclear phagocytosis in man? Chronobiol Int 5:81-83, 1988.
Bureau JP, Coupe M, Labreque G, Vago P: Chronobiologie de l'inflammation. Path Biol 35:942-950, 1987.
Bureau JP, Garelly L, Vago P: Nycthemeral variations on LPS- and BCG-induced PMN migration in normal mice. Int J Tissue React 13:203-206, 1991.
Chen JC, Ng CJ, Chiu TF, Chen HM: Altered neutrophil apoptosis activity is reversed by melatonin in liver ischemia-reperfusion. J Pineal Res 34:260-264, 2003.
Conti A, Maestroni GJM: Melatonin-induced immuno-opioids: role in lymphoproliferative and autioimmune diseases. Adv Pineal Res 7:83-100, 1994.
Cornelissen G, Halberg F: Introduction to chronobiology. Medtronic chronobiology Seminar No. 7, Library of Congress, Catalog Card No. 94-060580, 1994.
Csaba G: Presence in and effects of pineal indoleamines at very low level of phylogeny. Experientia 49:627-634, 1993.
Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabo C: Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 23:106-116, 1997.
Doherty DE, Haslett C, Fonnesen MG, Henson PM: Human monocyte adherence: a primary effect of chemotactic factors on the monocyte to stimulate adherence to human endothelium. J Immunol 138:1762-1771, 1987.
Dubocovich ML, Rivera-Bermudez MA, Gerdin MJ, Masana ML: Molecular pharmacology regulation and function of mammalian melatonin receptors. Front Biosci 8d:1093-1108, 2003.
Felegean A, Junie M, Baciu I: Effects of the electrolytic damage of the arcuate nucleus on the blood neutrophils phagocytic activity and phagocytic response. Rom J Physiol 34:75-82, 1997.
Forni G, Bindoni M, Santoni A, Belluardo N, Marchese AE, Giovarelli M: Radio frequency destruction of the tubero-infundibular region of hypothalamus permanently abrogates NK cell activity in mice. Nature 306:181-185, 1983.
Garelly L, Bureau JP, Labreque G: Temporal study of carrageenan-induced PMN migration in mice. Agents Actions 33:225-228, 1991.
Gatti G, Masera RG, Carignola R, Sartori ML, Margro E, Angeli A: Circadian-single-dependent enhancement of human natural killer cell activity by melatonin. J Immunol Res 2:108-116, 1990.
Halberg F: Temporal coordination of physiological function. Cold Spr. Harb Symp Quant Biol 25:289-310, 1960.
Hastings MH: The vertebrate clock: localisation connection and entrainment. In Redfern PH and Lemmer B (eds.): Physiology and Pharmacology of Biological Rhythms Springer 1997, pp. 1-21.
Haus E: Biologic rhythms in hematology. Pathol Biol 44 (Paris) :618-630, 1996.
Hriscu M: Modulatory factors of circadian phagocytic activity. Doctoral thesis, Babes-Bolyai University, Cluj-Napoca, 2003.
Hriscu M, Saulea G: Phagocytic activity and adherence of neutrophils in rats under light-dark alternation and constant light. Physiology National Conference, Cluj-Napoca 2002.
Hriscu M, Saulea G, Vidrascu N, Baciu I: Effects of monosodium glutamate on blood neutrophils phagocytic activity and phagocytic response in mice. Rom J Physiol 34:95-101, 1997.
Hriscu M, Saulea G, Vidrascu N, Baciu I: Circadian rhythm of phagocytosis in mice. Rom J Physiol 35:315-319, 1998.
Illnerova H, Vanecek J: Response of rat pineal serotonin N-acetyltransferase to one minute light pulse at different hight times. Brain Res 167:431-434, 1979.
Klein DC, Weller JL: Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science 169:1093-1095, 1970.
Lesnikov VA, Cvetkova IP: Stereotaxic coordinates of the hypothalamus in mice (In Russian). Fiziol Zurn 71:798-804, 1985.
Lesnikov VA, Adjieva SB, Korneva EA: Endogenous splenic colony-formation in mice in experimental pathology of the CNS (In Russian). Patol Fiziol 6:14-17, 1989.
Lin YL, Tai MY, Tsai YF: Morphological changes in the hypothalamic neurons of female rats exposed to continuous illumination. Chin J Physiol 33:291-298, 1990.
Lopez C., J.L. deLyra, R. Pekelmann Markus, M. Mariano: Circadian rhythm in experimental granulomatous inflammation is modulated by melatonin. J. Pineal Res. 23: 72-78, 1997.
Lotufo CM, Lopes C, Dubocovich ML, Farsky SH, Markus LP: Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. Eur J Pharmacol 430:351-357, 2001.
MacGregor RR, Spagnuolo P, Lentnek A: Inhibition of granulocyte adherence by ethanol prednisone and aspirin measured with an assay system. N Engl J Med:642-646, 1974.
MacGregor RR, Macarak E, Kefalides N: Comparative adherence of granulocytes to endothelial monolayer and nylon fiber. 61:697-702, 1978.
Maestroni GJM, Conti A: The pineal neurohormone melatonin stimulates activated CD4+ Thy-1+ cells to release opioid agonists with immunoenhancing and anti-stress properties. J Neuroimmunomodul 28:167-176, 1990.
Maestroni GJM, Conti A: Melatonin and the immuno-hematopoietic system therapeutic and adverse pharmacological correlates. J Neuroimmunomodul 3:325-332, 1996.
Maestroni GJM, Conti A, Pierpaoli W: Role of the pineal gland in immunity: Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13:19-30, 1986.
Maestroni GJM, Conti A, Pierpaoli W: Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin Exp Immunol 68:384-391, 1987.
Morrey KM, McLachlan JA, Serkin CD, Bakouche O: Activation of human monocytes by the pineal hormone melatonin. J Immunol 153:2671-2680, 1994.
Olsen LF, Kummer U, Kindzelskii AL, Petty HR: A model of the oscillatory metabolism of activated neutrophils. Biophys J 84:69-81, 2003.
Pickard GE: The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection. J Comp Neurol 211:65-83, 1982.
Pickard GE, Turek FW: The hypothalamic paraventricular nucleus mediates the photoperiodic control of reproduction but not the effects of light on the circadian rhythm of activity. Neurosci. Lett. 43: 67-72, 1983.
Pieri C, Recchioni R, Moroni F, Marcheselli F, Marra M, Marinoni S, Di Primio R: Melatonin regulates the respiratory burst of human neutrophils and their depolarization. J Pineal Res 24:43-49, 1998.
Pierpaoli W, Yi CX: The involvement of pineal gland in immunity and aging: I. Thymus-mediated immunoreconstituting and antiviral activity of thyrotropin-releasing hormone. J Neuroimmunol 27:99-109, 1990.
Poirel VJ, Masson-Pevet M, Pevet P, Gauer F: MT1 melatonin receptor mRNA expression exhibits a circadian variation in the rat suprachiasmatic nuclei. Brain Res 946:64-71, 2002.
Pownall R, Kabler PA, Knapp MS: The time of day of antigen encounter influences the magnitude of the immune response. Clin Exp Immunol 36:347-354, 1979.
Recchioni R, Marcheselli F, Moroni F, Gaspar R, Damjanovich S, Pieri C: Melatonin increases the intensity of respiratory burst and prevents L-selectin shedding in human neutrophils in vitro. Biochem Biophys Res Commun 252:20-24, 1998.
Reiter RJ, Garcia JJ, Pie J: Oxidative toxicity in models of neurodegeneration: responses to melatonin. Restor Neurol Neurosci 12:135-142, 1998.
Rodriguez AB, Lea RW: Effect of pinealectomy upon the nonspecific immune response of the ring dove (Streptopelia risoria). J Pineal Res 16:159-166, 1994.
Rodriguez AB, Ortega E, Lea RW, Barriga C: Melatonin and the phagocytic process of heterophils from the ring dove (Streptopelia risoria). Molec Cell Biochem 168:185-190, 1997.
Rodriguez AB, Marchena JM, Nogales G, Duran J, Barriga C: Correlation between the circadian rhythm of melatonin phagocytosis and superoxide anion levels in ring dove heterophils. J Pineal Res 26:35-42, 1999.
Rodriguez AB, Terron PM, Duran J, Ortega E, Barriga C: Physiological concentrations of melatonin and corticosterone affect phagocytosis and oxidative metabolism of ring dove heterophils. J Pineal Res 31:31-38, 2001.
Saeb-Parsy K, Dyball RE: Defined cell groups in the rat suprachiasmatic nucleus have different day/night rhythms of single-unit activity in vivo. J Biol Rhythms 18:26-42, 2003a.
Saeb-Parsy K, Dyball RE: Responses of cells in the rat suprachiasmatic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle. J Neuroendocrinol 15:895-903, 2003b.
Sainz RM, Mayo JC, Uria H, Kotler M, Antolin I, Rodriguez C, Menendez-Pelaez A: The pineal hormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J Pineal Res 19:178-188, 1995.
Sanchez S, Paredes SD, Martin MI, Barrigua C, Rodriguez AB: Effect of tryptophan administration on circulating levels of melatonin and phagocytic activity. J Appl Biomed 2:169-177, 2004.
Saulea G: The olfactory bulb and immunity. Doctoral thesis, University of Medicine and Pharmacy, Cluj-Napoca 1999.
Saulea G, Hriscu M, Vidrascu N, Baciu I: Influence of bilateral olfactory bulbectomy on the circadian rhythm of phagocytic activity in mice. Rom J Physiol 35:309-314, 1998.
Swanson LW, Cowan WM: The efferent connections of the suprachiasmatic nucleus of the hypothalamus. J Comp Neurol 160:1-12, 1975.
Swoyer J, Haus E, Sackett-Lundeen L: Circadian reference values for hematologic parameters in several strains of mice. Prog Clin Biol Res 227 A:281-296, 1987.
Vanecek J: Cellular Mechanisms of Melatonin Action. Phys Rev 78:687-721, 1998.
Williams LM, Hannah LT, Hastings MH, Maywood ES: Melatonin receptors in the rat brain and pituitary. J Pineal Res 19:173-177, 1995.
Yellon SM, Tran LT: Photoperiod reproduction and immunity in select strains of inbred mice. J Biol Rhythms 7:65-67, 2002.
Roy B, Singh R, Kumar S, Rai U: Diurnal variation in phagocytic activity of splenic phagocytes in freshwater teleost Channa punctatus: melatonin and its signaling mechanism. J Endocrinol 199:471-480, 2008.
Hriscu ML: Modulatory factors of circadian phagocytic activity. Reversal of Aging: Resetting the Pineal Clock, Book Series: Ann NY Acad Sci 1057:403-430, 2006.