title: Tumor necrosis factor-alpha administration increases Kupffer cell cyclic adenosine monophosphate levels.
abstract: Although studies have indicated that both Kupffer cell cyclic adenosine monophosphate (cAMP) and circulating TNF levels increase following trauma-hemorrhage and resuscitation, it remains unknown whether the elevated TNF levels are responsible for the increased Kupffer cell cAMP levels. To determine this, recombinant murine TNF-alpha (1.2 x 10(7) U/mg) was infused intravenously (.25 mg/kg body wt) over 30 min in normal rats. At 1 h after TNF-alpha or vehicle infusion, Kupffer cells and hepatocytes were isolated and cAMP levels were determined by radioimmunoassay. The levels of cAMP in the spleen and kidney were also measured. In addition, the maximal binding capacity and affinity of beta-adrenergic receptors were determined in Kupffer cells and hepatocytes by using [125I]iodopindolol. To determine whether there is any correlation between Kupffer cell cAMP and prostaglandin E2 (PGE2) or epinephrine, plasma levels of catecholamines and PGE2 were measured. The results indicated that TNF-alpha infusion significantly increased Kupffer cell cAMP levels while hepatocyte cAMP levels were not altered. Moreover, cAMP levels also increased in the macrophage/lymphocyte-rich spleen but were not altered in the kidney. Kupffer cell beta-receptor binding characteristics were not significantly affected by TNF-alpha infusion. In contrast, TNF-alpha administration markedly increased plasma levels of PGE2 and epinephrine. Thus, the elevated Kupffer cell cAMP levels induced by TNF-alpha are not due to upregulation of beta-adrenergic receptors, but may be associated with the elevated levels of circulating PGE2 and/or epinephrine.
authors.affiliation: Department of Surgery, Michigan State University, East Lansing 48824, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: S M
authors.initials: SM
authors.lastname: Tait
authors.forename: Z F
authors.initials: ZF
authors.lastname: Ba
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000097:blood*; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000097:blood*; D007262:Infusions, Intravenous; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D015232:Dinoprostone