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.