Chemotactic activity of plasma and lung lymph in sheep with endotoxemia: effect of hydroxyl radical scavengers.

The formation and release of circulating chemoattractants has been considered to be responsible for the initial pulmonary leukostasis and subsequent pulmonary vascular injury seen with endotoxemia. Oxygen radicals released from granulocytes can produce these factors. Our purpose was (1) to determine whether chemotaxins are released with endotoxemia and whether the lung is the source of these factors and (2) if there is a cause and effect relationship between the release of chemoattractants and the lung injury. Lung lymph flow, QL, lymph protein clearance, and vascular pressures were used to monitor lung vascular integrity. Escherichia coli endotoxin was infused into 12 sheep. Six sheep were pretreated with dimethyl thiourea (DMTU), a scavenger of hydroxide ion radicals. Chemotactic activity (CA) of plasma and lung lymph was determined during baseline, the pulmonary hypertensive phase, and the permeability phase of the lung injury. It was found that endotoxemia was associated with generation of a granulocyte chemotactic factor in plasma but not in lung lymph. The peak increase in plasma CA occurred after the early pulmonary leukostasis. Pretreatment with DMTU eliminated the increased CA but had no effect on the initial leukopenia or the lung injury. It was concluded that (1) the lung is not the major source of increased CA after endotoxin and (2) increased plasma CA occurs but does not appear to be causative of the initial pulmonary leukostasis or the granulocyte-induced lung injury.