Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep. Sone, Yasuyuki, Vladimir B Serikov, and Norman C Staub Sr. Cardiovascular Research Institute, University of California, San Francisco, California 94143
APStracts 6:0266A, 1999.
We recently showed that we can selectively and safely deplete most (average 85 %) of the pulmonary intravascular macrophages in sheep by intravenously infusing liposomes containing dichloromethylene bisphosphonate. After a one hour stable baseline, we made a six hour comparison following a 30 minute intravenous endotoxin infusion (1 *g/kg) between six anesthetized control lambs and six anesthetized lambs, whose intravascular macrophages had been depleted 24 hours previously. Three of the control lambs had been macrophage-depleted and allowed to recover their intravascular macrophage population for two or more weeks. Following depletion, both the early and late pulmonary arterial pressure rises were dramatically attenuated. Our main interest, however, was in the acute lung microvascular injury response. The early and late rises in lung lymph flow and the increase in lung lymph protein clearance (lymph flow _ lymph/plasma protein concentration ratio) were more than 90 % attenuated. We conclude the pulmonary intravascular macrophages are responsible for most of the endotoxin-induced pulmonary hypertension and increased lung microvascular leakiness in sheep, although the unavoidable injury of other intravascular macrophages by the depletion regime may also contribute something. 

Received 11 January 1999; accepted in final form 11 June 1999.
APS Manuscript Number A021-9.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 22 June 1999