Neural Adrenergic/Cyclic AMP Regulation of the Immunoglobulin E Receptor α-Subunit Expression in the Mammalian Pinealocyte: A NEUROENDOCRINE/IMMUNE RESPONSE LINK?

Surajit Ganguly,Cristina Grodzki,David Sugden,Morten Møller,Sandra Odom,Pascaline Gaildrat,Igal Gery,Reuben P Siraganian,Juan Rivera,David C Klein

doi:10.1074/jbc.m705950200

Abstract

The high affinity immunoglobulin E receptor (FcepsilonRI) complex is dedicated to immunoglobulin E-mediated allergic responses. Expression of the FcepsilonRI receptor is thought to be relatively stable and limited to mast cells, basophils, eosinophils, monocytes, Langerhans cells, platelets, and neutrophils. We now report that the FcepsilonRIalpha and FcepsilonRIgamma polypeptides are expressed in the pinealocyte, the melatonin-secreting cell of the pineal gland. Moreover, Fcer1a mRNA levels increased approximately 100-fold at night to levels that were higher than in other tissues examined. Pineal FcepsilonRIalpha protein also increased markedly at night from nearly undetectable daytime levels. Our studies indicate that pineal Fcer1a mRNA levels are controlled by a well described neural pathway that controls pineal function. This pathway includes the master circadian oscillator in the suprachiasmatic nucleus and passes through central and peripheral structures. The circadian expression of FcepsilonRIalpha in the pineal gland is driven by this neural circuit via an adrenergic/cyclic AMP mechanism. Pineal FcepsilonRIalpha and FcepsilonRIgamma may represent a previously unrealized molecular link between the neuroendocrine and immune systems.

Highlights

From the ‡Section on Neuroendocrinology, Office of the Scientific Director, NICHD, National Institutes of Health, Bethesda, Maryland 20892, the §Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the ¶Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, the ʈDivision of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King’s
Fcer1a mRNA and Fc⑀RI␣ Protein Occur in the Pineal Gland— Fcer1a mRNA and Fc⑀RI␣ protein were detected in pineal glands removed at midnight (Fig. 1, A and B) but not in those removed at noon
Western blot studies indicated that the immunopositive proteins in rat basophilic leukemia (RBL) cell and in the pineal gland were similar in size (ϳ50kDa, Fig. 1B)

Summary

The abbreviations used are

Fc⑀RI, high affinity immunoglobulin E receptor; NE, norepinephrine; ISO, isoproterenol; ZT, zeitgeber time; SCG, superior cervical ganglion; RBL, rat basophilic leukemia; SCN, suprachiasmatic nucleus; PBS, phosphate-buffered saline; BisTris, 2-[bis(2-hydroxyethyl) amino]-2-(hydroxymethyl)propane-1,3-diol. ␣- and ␥-Chains of Fc⑀RI in the Mammalian Pinealocyte analysis of gene expression in the pineal gland, a tissue not known to be involved in the immune response. This tissue is recognized as being dedicated to the generation of the daily rhythm in circulating melatonin, a conserved feature of vertebrate biology [9]. Our microarray results were surprising because they suggested that there is a daily rhythm in Fcer1a expression in the pineal gland and that nighttime levels are higher than in other tissues. Our findings provide justification to consider that Fc⑀RI might provide a unique molecular link between the neuroendocrine and immune systems

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION