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L-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages in vitro

¹ Dept of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, ² Dept of Pulmonology, University Hospital Groningen, Oostersingel 59, Groningen, and ³ Dept of Pharmacology and Pathophysiology, Utrecht University, Utrecht, the Netherlands

CORRESPONDENCE: G. Folkerts, Dept of Pharmacology and Pathophysiology, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. Fax: 31 302537420

Keywords: alveolar macrophage, human, monocyte, nitric oxide

Received: December 1, 2000
Accepted March 16, 2001

This study was funded by a research grant from the Netherlands Asthma Foundation no. 95.28.

Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate l-;arginine, and putative NOS inhibiting factors present in foetal serum preparations, both alveolar macrophages (AM) and monocyte derived macrophages (MDM) were incubated in various circumstances.

Nitrite production measured using stimulated AM was typically <5 pmol·min^–1·10^–6 cells. A range of stimuli were tested, but without result. Furthermore, incubation of MDMs with normal human serum or purified bovine serum albumin instead of foetal calf serum failed to enhance NO production. Moreover, neither the use of arginase inhibitors nor the addition of surplus l-;arginine resulted in an increased NO synthesis. Interestingly, addition of the NOS intermediate N-;hydroxy-;l-;arginine (100 µM) to AM led to nitrite release, which was unaffected by the NOS inhibitor amino guanidine showing that this effect is NOS independent.

It is concluded that the limited nitric oxide production of human macrophages in vitro can neither be explained by limited availability of l-;arginine, nor by nitric oxide synthase inhibiting substances in foetal serum. Furthermore, it is shown that nitrite release from N-;hydroxy-;l-;arginine by alveolar macrophages is nitric oxide synthase independent.

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