Endotoxin stimulates the expression of group II PLA2 in rat lung in vivo and in isolated perfused lungs.
Injection of endotoxin in vivo leads to increased phospholipase A2 (PLA2) activity in the lung, but neither the type(s) of PLA2 involved nor the importance of blood components and/or different inflammatory cytokines has been clarified. In the present study, injection of endotoxin in rats caused increased lung levels of group II PLA2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta mRNA, while group I PLA2 mRNA levels were unaffected. The augmented group II PLA2 mRNA levels corresponded to a rise in membrane-associated PLA2 enzymatic activity that was inhibited by rutin, an inhibitor of group II PLA2. In blood-free, salt-perfused lungs, addition of endotoxin to the perfusate caused elevated group II PLA2, TNF-alpha, and IL-1 beta mRNA levels and release of PLA2 and TNF-alpha activity into the perfusate, and when instilled intratracheally, endotoxin caused increased PLA2 activity in the lung tissue. It is concluded that 1) endotoxin stimulates group II PLA2, but not group I PLA2, in rat lung cells, 2) this stimulation is accompanied by increased expression of TNF-alpha and IL-1 beta, and 3) endotoxin-induced PLA2 activation and cytokine production in the lung are not dependent on circulating blood components.
Ljungman
A G
AG
Department of Occupational and Environmental Medicine, Faculty of Health Sciences, University of Linköping, Sweden.
Tagesson
C
C
Lindahl
M
M
D000818:Animals; D001483:Base Sequence; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D015335:Molecular Probes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2