Comparison of response of bovine and porcine pulmonary arterial endothelial cells to monocrotaline pyrrole.
Monocrotaline (MCT)-induced vascular injury in liver and lung may be caused by interaction of MCT metabolites such as monocrotaline pyrrole (MCTP) with vascular cells. Responses of bovine and porcine pulmonary artery endothelial cells (BECs and PECs, respectively) to a single administration of MCTP were compared. MCTP caused a delayed and progressive release of lactate dehydrogenase (LDH) activity from BECs and a gradual decrease in monolayer cellularity. Surviving cells became markedly hypertrophic. PECs were less sensitive to the cytolytic effects of MCTP, showing minimal cell detachment and little release of LDH activity. However, monolayer cellularity, as assessed by PEC enumeration, decreased in a dose-dependent manner. Hypertrophy of surviving PECs was less pronounced than in BECs. MCTP caused enhanced release of prostacyclin from monolayers of BECs and PECs exposed to 10 micrograms MCTP/ml, and concentrations of 0.5 microgram/ml or greater caused equivalent reduction in colony-forming efficiency in both cell types. In summary, whereas BECs were more susceptible to the cytolytic and hypertrophic effects of MCTP, BECs and PECs responded similarly with regard to prostacyclin release and were equally sensitive to the cytostatic effects of this compound.
Reindel
J F
JF
Department of Pathology and of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Hoorn
C M
CM
Wagner
J G
JG
Roth
R A
RA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D016686:Monocrotaline / Q000031:analogs & derivatives* / Q000633:toxicity; D013552:Swine
C014114:monocrotaline pyrrole; D015121:6-Ketoprostaglandin F1 alpha; D016686:Monocrotaline; D007770:L-Lactate Dehydrogenase