Human alveolar macrophages and monocytes as a source and target for nitricoxide

Nitric oxide (NO) is synthesized in the lung and this free radical particip ates in a wide array of regulatory, protective, and adverse interactions wi th cells. Both excess NO and its insufficiency have been implicated in the pathogenesis of numerous lung diseases with inflammatory components. Much o f 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 a re generally low [J. Leukocyte Biol. 58 (1995) 643]. The regulation of macr ophage 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 o f NO as toxic pro-inflammatory or protective anti-inflammatory agent is unr esolved. While not a major source of NO in the human lung, the alveolar mac rophage is an important producer of cytokines and this production may be mo dified by NO. Clear evidence of abnormalities in NO levels in the lungs of patients with asthma, bronchiectasis, viral infections, lung cancer and pri mary pulmonary hypertension (PPH) has been documented. Elevated inflammator y cytokines and oxidant production have been associated with all of these d isease states. In terms of cytokine production, NO has been shown to decrea se nuclear factor kappa B (NF-kappaB) activation. However, oxidants may int eract with NO to form toxic compounds (e.g., NO combines with superoxide an ion to form peroxynitrite). Furthermore, such reactions may decrease the av ailability of NO for blocking inflammatory cytokine production. Thus, avail able data suggests that a multiplicity of factors affect NO regulatory prop erties in inflammatory situations. (C) 2001 Elsevier Science B.V. All right s reserved.