Radiodetoxified endotoxin-induced tolerance alters monocyte but not neutrophil CD11b and CD18 expression in response to lipopolysaccharide
T. P. Connall, J. Zhang, N. D. Vaziri, R. J. Schwartz, C. J. Kaupke, F. Oveisi and S. E. Wilson
Department of Surgery, University of California-Irvine.
OBJECTIVES: To test the hypothesis that pretreatment with radiodetoxified
endotoxin (RDE) may mitigate the deleterious effects of subsequent
infection, in part by modifying leukocyte adhesion receptor expression, and
to investigate the cellular mechanisms of endotoxin tolerance induced by
RDE. DESIGN: To assess the effect of RDE pretreatment on mortality from
bacterial peritonitis, rats were implanted with an intraperitoneal,
barium-fecal inoculum at intervals of 0, 1, 3, and 5 days after RDE
injection. Experiments were then conducted to test the effect on leukocyte
adhesion receptor expression. Two groups of mice received saline solution,
and one group, RDE. After 72 hours, one group received saline solution
(saline/saline group), the others, lipopolysaccharide (LPS) (saline/LPS and
RDE/LPS groups). Peripheral leukocytes were obtained 1 hour after injection
and were analyzed for CD11b and CD18 expression by flow cytometry. SETTING:
Laboratory animal study. RESULTS: Survival rates were not improved in rats
that were pretreated with RDE 0 and 24 hours before inoculum (0% and 7%,
respectively). In rats that were pretreated 72 hours and 120 hours before
inoculum, 47% (P < .01) and 60% (P < .01) survived, respectively.
CD18 expression on polymorphonuclear leukocytes increased twofold in the
RDE/LPS (mean +/- SEM, 300.3 +/- 32.9) and the saline/LPS (mean +/- SEM,
360.4 +/- 59.9) groups compared with controls (mean +/- SEM, 176.4 +/-
18.9) (P < .05). CD11b expression on polymorphonuclear leukocytes
increased threefold in the RDE/LPS (mean +/- SEM, 91.3 +/- 8.1) and the
saline/LPS (mean +/- SEM, 89.8 +/- 11.4) groups compared with controls
(mean +/- SEM, 32.1 +/- 1.8) (P < .05). CD18 expression on monocytes
decreased in the saline/LPS group (mean +/- SEM, 134.2 +/- 14.2) and was
unchanged in the RDE/LPS group (mean +/- SEM, 200.2 +/- 17.2) compared with
controls (mean +/- SEM, 217.6 +/- 16.5) (P < .05). CD11b expression on
monocytes decreased in the saline/LPS group (mean +/- SEM, 25.8 +/- 2.2)
and was unchanged in the RDE/LPS group (mean +/- SEM, 36.4 +/- 0.9)
compared with controls (mean +/- SEM, 39.7 +/- 3.9) (P < .05).
CONCLUSIONS: Radiodetoxified endotoxin reduces mortality rates from
bacterial peritonitis when given at least 72 hours prior to a bacterial
inoculum. Tolerance to subsequent LPS challenge is associated with an
abrogation of the reduced peripheral monocyte CD11b and CD18 expression
observed in native LPS-stimulated mice but is not associated with changes
in polymorphonuclear leukocyte CD11b and CD18 expression. The mechanism of
the observed RDE-induced monocyte hyporesponsiveness to LPS and its
possible protective effect is uncertain and requires further investigation.
