Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G

While the critical role of reactive oxygen intermediates (ROI) in the micro bicidal activity of polymorphonuclear granulocytes is well established, the function of the nonoxidative effector mechanisms in vivo remains unclear. Here we show that mice deficient in the neutrophil granule serine proteases elastase and/or cathepsin G are susceptible to fungal infections, despite normal neutrophil development and recruitment. The protease deficiencies bu t not the absence of ROI leads to enhanced resistance to the lethal effects of endotoxin LPS, although normal levels of TNF alpha are produced. The da ta demonstrate a critical role of the nonoxidative effector mechanisms of n eutrophils in host immunity and immunopathology and identify elastase and c athepsin G as effecters in the endotoxic shock cascade downstream of TNF al pha.