Mediators of pulmonary injury induced by inhalation of bacterial endotoxin.
The purpose of this study has been to further define the pathophysiologic aspects of lung injury caused by the inhalation of endotoxin (LPS) using the morphometric approach to identify mediators that influence distal lung structure and function. Hamsters were divided into 3 groups 24 h prior to low dose LPS inhalation exposure (4 micrograms/m3 for 5 h): (1) pretreated with cobra venom factor to deplete complement in vivo, (2) pretreated with indomethacin to block prostaglandin production, and (3) untreated control group. Both pretreatments abolished LPS-induced decreases in lung volume as well as increases in capillary PMN and platelets seen in untreated control animals. Neither pretreatment had any effect on the LPS-induced decreases of other capillary leukocytes. Similarly, both methods of pretreatment failed to block increases in cellular interstitium of distal capillary septa induced with LPS alone. LPS provoked changes in capillary endothelium, especially seen as an increase in numerical density of endothelial pinocytotic vesicles. Decomplementation failed to alter this increase, but indomethacin pretreatment blocked the effect. Neither treatment had any effect on their size. Low dose LPS inhalation also altered pulmonary capillary permeability to a 125I-BSA probe, which was found in significantly greater amounts in LPS-exposed lungs than in those of saline aerosol control lungs, but was not present in the air space as evidenced by negligible counts in bronchoalveolar lavages. It is evident that endotoxin on the epithelial side of the air-blood barrier leads to changes on the other side of that barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Burrell
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R
Department of Microbiology, West Virginia University Medical Center, Morgantown 26506.
Lantz
R C
RC
Hinton
D E
DE
D000818:Animals; D001792:Blood Platelets; D001810:Blood Volume; D002196:Capillaries / Q000648:ultrastructure; D002199:Capillary Permeability; D003165:Complement System Proteins / Q000032:analysis; D006224:Cricetinae; D004546:Elapid Venoms / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D004754:Enterobacter; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008171:Lung Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D011453:Prostaglandins / Q000097:blood; D011652:Pulmonary Circulation
D004546:Elapid Venoms; D004731:Endotoxins; D008070:Lipopolysaccharides; D011453:Prostaglandins; C016310:cobra venom factor; D003165:Complement System Proteins; D007213:Indomethacin