Relative contribution of hemopoietic and pulmonary parenchymal cells to lung inducible nitric oxide synthase (iNOS) activity in murine endotoxemia

Acute lung injury is an important feature of sepsis and increased iNOS expr ession and NO production contribute to the pathogenesis of this syndrome. W e generated bone marrow-transplanted chimeric mice with iNOS expression lim ited to either inflammatory or pulmonary parenchymal cells, and assessed pu lmonary iNOS activity and systemic levels of NO metabolites in an endotoxem ic model of sepsis, We found that while both pulmonary parenchymal cells an d inflammatory cells contribute to the increased lung NOS activity in endot oxemia, pulmonary parenchymal cells contribute to a significantly greater d egree. Using measurement of plasma NOx-, whole body NO production was asses sed in this model, We found that the main source of NOx- was again, parench ymal cells and not inflammatory cells, This is the first study to demonstra te that most of the increased NO production in this model of endotoxemic se psis derives from parenchymal cells rather than inflammatory cells. (C) 200 1 Academic Press.