Pentoxifylline does not attenuate acute lung injury in the absence of granulocytes.
Pentoxifylline (PTX), a methylxanthine, can suppress polymorphonuclear leukocyte (PMN) activation and attenuate sepsis-induced acute lung injury. We investigated whether PTX prevents non-PMN-dependent lung injury. First we studied four groups of granulocyte-depleted guinea pigs (control, PTX, Escherichia coli, and E. coli + PTX). Lung injury was assessed by wet-to-dry lung weight (W/D) ratio and lung tissue-to-plasma 125I-albumin ratio (albumin index, AI). The E. coli group showed a significant increase in the lung W/D ratio and AI compared with the control and PTX groups. However, PTX did not prevent the E. coli-induced increase in the lung W/D ratio and AI. Next we investigated the effects of PTX on endothelial cell monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels. Whereas E. coli lipopolysaccharide (LPS) alone increased the endothelial permeability, PMNs added to the endothelial monolayers and exposed to LPS enhanced the increase. PTX attenuated the permeability increase mediated by LPS-exposed PMNs. PTX did not prevent the LPS-induced increase in permeability when PMNs were not present, although PTX increased endothelial cell cAMP levels. These data demonstrate that 1) PTX does not prevent lung injury in granulocyte-depleted guinea pigs; 2) PTX does not prevent LPS-induced increases in endothelial cell permeability, despite increased cAMP levels; and 3) PTX attenuates PMN-dependent increases in endothelial cell permeability.
Yonemaru
M
M
Department of Medicine, Stanford University School of Medicine, California 94305.
Hatherill
J R
JR
Hoffmann
H
H
Zheng
H
H
Ishii
K
K
Raffin
T A
TA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D006098:Granulocytes / Q000502:physiology*; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000494:pharmacology; D008171:Lung Diseases / Q000503:physiopathology*; D010431:Pentoxifylline / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D012711:Serum Albumin, Radio-Iodinated
D008070:Lipopolysaccharides; D012711:Serum Albumin, Radio-Iodinated; D000242:Cyclic AMP; D010431:Pentoxifylline