Effect of chronic endotoxemia on concanavalin A-stimulated inositol lipid metabolism in rat splenocytes.
The effect of a chronic, nonlethal infusion of endotoxin (ET) on the phosphatidylinositol (PI) cycle in rat splenocytes was evaluated. Rats were infused intravenously with sterile saline or Escherichia coli ET (0.1 mg/100 g body weight/24 hr) for 30 hr via subcutaneously implanted osmotic pumps. The splenocytes were then labeled in vitro for 90 min with [32P]PO4 or for 3 hr with [3H]myoinositol to assess the status of the resynthesis and degradative parts of the PI cycle, respectively. PI cycle activity was depressed in splenocytes of ET-infused rats as evidenced by a 25% reduction in the incorporation of [32P]PO4 into phosphatidic acid (PA), PI, and the polyphosphoinositides and by a similar decrease in the production of [3H]inositol phosphates. Stimulation of splenocytes with concanavalin A (Con A) resulted in dose-dependent increases in the incorporation of [32P]PO4 into PA and PI and in the production of [3H]inositol phosphates, indicating that Con A stimulates the PI cycle in these cells. The Con A-stimulated increase in inositol phosphate production was higher in splenocytes from ET-infused rats. We have previously shown that splenocytes from rats infused for 30 hr with ET exhibit a decreased blastogenic responsiveness to Con A and lipopolysaccharide [Spitzer et al., Proc. Soc. Exp. Biol. Med. 186,27, 1987]. The present data do not support the notion that inositol lipid-mediated signaling mechanisms are solely responsible for the expression of the appropriate functional response and suggest that in ET-infused rats there is an uncoupling of the initial response to Con A (i.e., the production of inositol lipid-derived second messengers) and the long-term (i.e., mitogenic) response.
Hagar
A F
AF
Department of Physiology, L.S.U. Medical Center, New Orleans 70112.
Rodriguez de Turco
E B
EB
Spitzer
J A
JA
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D015536:Down-Regulation; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D008297:Male; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000378:metabolism*
D004731:Endotoxins; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D003208:Concanavalin A; D011493:Protein Kinase C