Environmental Health Perspectives 105, Supplement 5, September 1997

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Expression of Inducible Nitric Oxide Synthase and Formation of Nitric Oxide by Alveolar Macrophages: An Interspecies Comparison

Natalie K. Jesch, 1 Martina Dörger, 1 Georg Enders, 1 Gabriele Rieder, 1 Claus Vogelmeier, 2 Konrad Messmer, 1 and Fritz Krombach 1

1 Institute for Surgical Research, 2 Department of Internal Medicine I, Klinikum Grosshadern, University of Munich, Munich, Germany

Abstract
Nitric oxide (NO) is suggested to play a role in mediating pulmonary injury. However, interspecies differences appear to exist in the ability of alveolar macrophages (AM) to express the inducible nitric oxide synthase (iNOS) and to generate NO. The purpose of this study was to compare iNOS expression and NO production by rat, hamster, monkey, and human AM using the identical experimental conditions in vitro . As AM donors, CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were used. The AM were obtained by bronchoalveolar lavage and stimulated in vitro with various concentrations and combinations of lipopolysaccharide (LPS) and interferon- gamma (IFN- gamma ). The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction. The expression of iNOS in AM was detected using immunocytochemistry and immunoblotting. The expression of iNOS mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rat AM, stimulated with either LPS or IFN- gamma , produced nitrite in a time- and dose-dependent manner. Combination of LPS and IFN- gamma resulted in a significantly enhanced nitrite formation. However, none of the treatments was able to induce hamster, monkey, or human AM to release measurable amounts of nitrite. Whereas expression of iNOS protein was only detected in stimulated rat AM, expression of iNOS mRNA was found in unstimulated and stimulated rat AM, slightly in stimulated hamster AM, but not in monkey and human AM. In conclusion, our findings point to distinct regulatory mechanisms of the NO pathway in AM from these four different species. -- Environ Health Perspect 105(Suppl 4):1297-1300 (1997)

Key words : nitric oxide, inducible nitric oxide synthase, alveolar macrophages, species differences, rat, hamster, monkey, human

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 27 March 1997; accepted 7 May 1997.

The authors thank A-M. Allmeling and E. Schütze for their expertise and excellent assistance. This work was supported in part by a grant from the European Insulation Manufacturers Association (EURIMA).

Address correspondence to Dr. F. Krombach, Institut für Chirurgische Forschung, Klinikum Grosshadern, Marchioninistr. 15, D-81366 München, Germany. Telephone: 49 89 7095 4359. Fax: 49 89 7095 8897. E-mail: krombach@icf.med.uni-muenchen.de

Abbreviations used: AM, alveolar macrophage(s); BSA, bovine serum albumin; BAL, bronchoalveolar lavage; iNOS, inducible nitric oxide synthase; IFN- gamma , interferon- gamma ; LPS, lipopolysaccharide; NO, nitric oxide; mRNA, messenger ribonucleic acid; PBS, phosphate-buffered saline; RT-PCR, reverse transcriptase-polymerase chain reaction.

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Last Update: December 1, 1997