Role of gut flora on intestinal group II phospholipase A2 activity and intestinal injury in shock.
We previously showed that group II phospholipase A2 (PLA2-II), a secretory, bactericidal, and proinflammatory protein in intestinal crypts, is upregulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF) challenge. Here we examined whether germ-free environment (GF) or antibiotic treatment (ABX) affects the pathophysiological responses and intestinal PLA2-II activity after PAF (1.5 microg/kg) or LPS (8 mg/kg) injection. We found that LPS and PAF induced hypotension and mild intestinal injury in conventionally fed (CN) rats; these changes were milder in ABX rats, whereas GF rats showed no intestinal injury. PLA2-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA2-II activity, which was abrogated in GF and ABX rats. Recolonization of GF rats by enteral contamination restituted their PLA2-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA2-II activity are dependent on gut bacteria, and ABX and GF rats are less susceptible to LPS-induced injury than CN rats.
Rozenfeld
R A
RA
Department of Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614, USA.
Liu
X
X
DePlaen
I
I
Hsueh
W
W
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018407:Bacterial Physiological Phenomena; D001794:Blood Pressure / Q000187:drug effects; D005856:Germ-Free Life; D054501:Group II Phospholipases A2; D006400:Hematocrit; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2