Oxygen Metabolites from Lavage and Interstitial Lung Cells after Inhalation of Endotoxin in Guinea Pigs

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Abstract
Airborne endotoxins play a role in a variety of occupational diseases such as byssinosis and humidifier’s disease and are associated with pulmonary and systemic symptoms. An excess generation of oxygen free radicals (including superoxide anion, O––2) by inflammatory cells has been suggested in endotoxemia. We have studied the release of superoxide from guinea-pig lung lavage and interstitial cells and blood monocytes (BMs) at different times after an acute inhalation exposure to bacterial endotoxin. O––2 generation was measured by the O––2 dismutase-inhibitable reduction of ferricytochrome c, after stimulation with phorbol-myristate-acetate (PMA) or opsonized zymosan (OZ). After endotoxin exposure the spontaneous release of O––2 remained unchanged for the three cell types. From 4 h after exposure until 48 h afterwards, lung lavage cells produced more O––2 after PMA or OZ stimulation than did cells from unexposed guinea pigs. The pattern of O––2 generation by interstitial cells followed that of lung lavage macrophages. O––2 production remained unchanged in BMs at all times. These results suggest that endotoxin inhalation induced a priming of lavage and interstitial cells, mainly macrophages, associated with an increase in O––2 production. As O––2 production by BMs remained unchanged, this cell is unlikely to be responsible for the systemic symptoms seen after endotoxin inhalation.

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