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Neuropeptide Y Is Expressed by Rat Mononuclear Blood Leukocytes and Strongly Down-Regulated during Inflammation¹

Julia Holler^2,*, Anna Zakrzewicz^2,*, Andreas Kaufmann, Jochen Wilhelm, Gabriele Fuchs-Moll^*, Hartmut Dietrich^¶, Winfried Padberg^*, Jitka Kuncová^||, Wolfgang Kummer and Veronika Grau^3,*

^* Department of General and Thoracic Surgery, Laboratory of Experimental Surgery, and Institute for Anatomy and Cell Biology, University of Giessen Lung Center, Justus-Liebig-University Giessen, Giessen, Germany; Institute of Immunology, Philipps University Marburg, Marburg, Germany; Department of Pathology, and ^¶ Department of Internal Medicine (Nephrology), Justus-Liebig-University Giessen, Giessen, Germany; and ^|| Department of Physiology, Charles University Medical School Plze, Plze, Czech Republic

Neuropeptide Y (NPY), a classical sympathetic comediator, regulates immunological functions including T cell activation and migration of blood leukocytes. A NPY-mediated neuroimmune cross-talk is well conceivable in sympathetically innervated tissues. In denervated, e.g., transplanted organs, however, leukocyte function is not fundamentally disturbed. Thus, we hypothesized that NPY is expressed by blood leukocytes themselves and regulated during inflammation. NPY mRNA and peptide expression were analyzed in mononuclear leukocytes isolated from the blood vessels of healthy rat kidneys, as well as from the blood vessels of isogeneic and allogeneic renal grafts transplanted in the Dark Agouti to Lewis or in the Fischer 344 to Lewis rat strain combination. Depending on the donor strain, acute allograft rejection is either fatal or reversible but both experimental models are characterized by massive accumulation of intravascular leukocytes. Leukocytes, predominantly monocytes, isolated from the blood vessels of untreated kidneys and isografts expressed high amounts of NPY mRNA and peptide, similar to expression levels in sympathetic ganglia. During acute allograft rejection, leukocytic NPY expression drastically dropped to 1% of control levels in both rat strain combinations. In conclusion, NPY is an abundantly produced and tightly regulated cytokine of mononuclear blood leukocytes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ A part of this study was supported by the Czech Republic (Grant MSM 0021620819).

² J.H. and A.Z. equally contributed to this study.

³ Address correspondence and reprint requests to Prof. Dr. Veronika Grau, Department of General and Thoracic Surgery, Laboratory of Experimental Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Rudolf-Buchheim Strasse 7, D-35385 Giessen, Germany. E-mail address: Veronika.Grau{at}chiru.med.uni-giessen.de

⁴ Abbreviations used in this paper: NPY, neuropeptide Y; iNOS, inducible NO synthase; C_T, cycle threshold.