Human alveolar macrophages and monocytes as a source and target for nitric oxide.

Nitric oxide (NO) is synthesized in the lung and this free radical participates in a wide array of regulatory, protective, and adverse interactions with cells. Both excess NO and its insufficiency have been implicated in the pathogenesis of numerous lung diseases with inflammatory components. Much of the available data concerning the source and regulation of NO production is derived from rodent systems. However, the requirements for NO production are more stringent in human monocytes/macrophages than in rodent systems. In contrast to rodent macrophages, human moncytes/macrophages generally do not respond to cytokine triggers with NO production [J. Leukocyte Biol. 58 (1995) 643, J. Exp. Med. 181 (1995) 735] and if NO is detected the levels are generally low [J. Leukocyte Biol. 58 (1995) 643]. The regulation of macrophage NO in the human appears to be a more selective and variable process than that seen in the rodent macrophages. In the human lung, the function of NO as toxic pro-inflammatory or protective anti-inflammatory agent is unresolved. While not a major source of NO in the human lung, the alveolar macrophage is an important producer of cytokines and this production may be modified by NO. Clear evidence of abnormalities in NO levels in the lungs of patients with asthma, bronchiectasis, viral infections, lung cancer and primary pulmonary hypertension (PPH) has been documented. Elevated inflammatory cytokines and oxidant production have been associated with all of these disease states. In terms of cytokine production, NO has been shown to decrease nuclear factor kappa B (NF-kappaB) activation. However, oxidants may interact with NO to form toxic compounds (e.g., NO combines with superoxide anion to form peroxynitrite). Furthermore, such reactions may decrease the availability of NO for blocking inflammatory cytokine production. Thus, available data suggests that a multiplicity of factors affect NO regulatory properties in inflammatory situations.