UP-REGULATION OF KUPFFER CELL BETA-ADRENOCEPTORS AND CAMP LEVELS DURING THE LATE-STAGE OF SEPSIS

Although a burst of immunoresponsiveness may occur during the early st age of sepsis, late sepsis is characterized by severe immunodepression . In addition, although studies have shown that stimulation of macroph age beta-adrenoceptors results in an increase in cAMP and an associate d reduction in macrophage phagocytic activity, it remains unknown whet her Kupffer cell beta-adrenoceptor characteristics and cAMP levels are altered during polymicrobial sepsis. To study this, Sprague-Dawley ra ts were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h (i.e., the early stage of sepsis) or 20 h (late sepsis) after CLP o r sham operation, the liver was perfused with collagenase solution and Kupffer cells were isolated. beta-Adrenoceptor characteristics of the isolated Kupffer cells were determined using [I-125]iodopindolol, and basal levels of cAMP were measured by radioimmunoassay. The results i ndicate that while maximum binding capacity (B-max) of Kupffer cell be ta-adrenoceptors was not altered at 5 h, it increased significantly at 20 h after CLP. Similarly, basal levels of cAMP in Kupffer cells did not change at 5 h but increased markedly at 20 h after the onset of se psis. In contrast, the dissociation constant (Kd, l/affinity) of Kupff er cell beta-adrenoceptors was not significantly affected by sepsis at both 5 h and 20 h after CLP. Thus, upregulation of beta-adrenoceptors and increase in cAMP levels in Kupffer cells occur during the late st age of polymicrobial sepsis, and this may contribute to the depression of macrophage phagocytic function under such conditions. 0167-4889/98 /$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserv ed.