CELLULAR IMMUNOLOGY 131, 398-403 (1990) Expression of Cellular Effector Functions and Production of Reactive Nitrogen Intermediates: A Comparative Study Including T Lymphocytes, T-Like Cells, Neutrophil Granulocytes, and Mononuclear Phagocytes’ R. KELLER *J R. KEIST,* P. ERB,t T. AEBISCHER,~ G. DE LIBERO,~ M. BALZER,~~ 3 P. GROSCURTH,~~ AND H. U. KELLER++ *Institute for Immunology and Virology, University of Zurich, Switzerland; tlnstitute for Medical Microbiology, University of Basel, Switzerland; *Institute of Pathology, University Hospital, Zurich, Switzerland; §Basel Institute for Immunology, Basel, Switzerland; “Department of Anatomy, University of Zurich, Switzerland; and #Institute of Pathology, University of Bern, Switzerland Received June 21, 1990; accepted August 8. 1990 The ability of various cell types to secrete reactive nitrogen intermediates (RNI) upon functional activation was comparatively assessed. Neither in T lymphocyte clones mediating MHC class I or class II antigen-restricted killing via cu/fiT cell receptor (TcR) or MHC-unrestricted killing via y/6 TcR, nor in peripheral blood mononuclear cells expressing natural killer or lymphokine- activated killer activity, target cell lysis was associated with detectable RN1 production. Also, activated neutrophil granulocytes did not secreteRNI. In contrast, bone marrow-derived mono- nuclear phagocytes, activated to express tumoricidal activity, secreted marked RN1 activity. 0 1990 Academic Press, Inc. INTRODUCTION It was first demonstrated in 1987 that, on stimulation, vascular endothelial cells and mononuclear phagocytes release reactive nitrogen intermediates (RNI)3, in par- ticular, nitric oxide ( 1, 2). Extensive work performed in the meantime suggested that RNI, generatedby enzymatic cleavage of terminal guanidino nitrogen from L-arginine, may act asa second messenger in vascular, nervous, and immune systems and mediate ’ This study was supported by the Swiss National Science Foundation (Grant 3 l-257 17.88 to R.K., and Grant 3.035-087 to P.E.) and the Krebsliga des Kantons Ziirich (to R.K.). * To whom correspondence should be addressedat Immunobiology Research Group, Institute for Im- munology and Virology, University of Zurich, Birchstr. 95, CH-8050 Zurich, Switzerland. 3Abbreviations used: CD, cluster of differentiation, CP, Corynebacterium parvum; DMSO, dimethyl- sulfoxide; fNLPNTL, N-fo~yl-~-norleucyl-~-leucyl-~-phenylalanyl-~-norleucyl-~-tyrosy~-~-~ysine; H-7, I- (5-isoquinolinylsulfonyl)-2-methylpiperazine; hPBMC, human peripheral blood mononuclear cells; IFN-7, interferon-y; IL, interleukin; KLH, keyhole limpet hemocyanin; LAK, lymphokine-activated killer cells; LCMV, lymphocytic choriomeningitis virus; LPS, lipopolysaccharide; LTB,, leukotriene Bq; MHC, major histocompatibility complex; M$, mononuclear phagocytes,macrophages; NK, natural killer cells; NO, nitric oxide; NO;, nitrite; oAG, 1 -oleyl-2-acetylglycerol; PMA, phorbol- 12-myristate-13-acetate; RNI, reactive nitrogen intermediates; TcR, antigen-specific T cell receptor. 398 OOOS-8749/90 $3.00 CopyrigJtt 0 1990 by Academic F’ms, Inc. All rights of reproduction in any form reserved