and specific aims): The normal lung macrophage shows a desirable """"""""down-regulation"""""""" of proinflammatory response when encountering unopsonized inert environmental particles, allowing clearance of such particles without lung injury. The basis for this lung-protective down-regulation or how it is overcome during pulmonary inflammation is poorly understood. The central hypothesis is that a constitutively expressed type III NOS functions in normal AMs to down-regulate activation responses to unopsonized phagocytosis, primarily through NO-mediated inhibition of mitochondrial respiration needed for effective redox-based activation signaling.
The specific aims are to: 1) characterize the expression of NOS-III in normal and activated AMs; and 2) characterize the function of NOS-III in modulating AM response to inhaled particles.
| Ning, Y; Imrich, A; Goldsmith, C A et al. (2000) Alveolar macrophage cytokine production in response to air particles in vitro: role of endotoxin. J Toxicol Environ Health A 59:165-80 |
| Imrich, A; Ning, Y Y; Kobzik, L (1999) Intracellular oxidant production and cytokine responses in lung macrophages: evaluation of fluorescent probes. J Leukoc Biol 65:499-507 |
| Imrich, A; Kobzik, L (1997) Fluorescence-based measurement of nitric oxide synthase activity in activated rat macrophages using dichlorofluorescin. Nitric Oxide 1:359-69 |
