DIFFERENTIAL UP-REGULATION OF CIRCULATING SOLUBLE AND ENDOTHELIAL-CELL INTERCELLULAR-ADHESION MOLECULE-1 IN MICE

Although circulating levels of soluble intercellular adhesion molecule -1 (sICAM-1) are frequently used as art indicator of the severity of d ifferent immune, inflammatory, or neoplastic diseases, little is known about the factors that govern plasma sICAM-1 concentration and its re lationship to the membranous for-nt of ICAM-1 (mICAM-1) expressed on v ascular endothelial cells, Plasma sICAM-1 concentration (measured by e nzyme-linked immunosorbent assay) aid mICAM-1 expression (measured usi ng the dual radiolabeled monoclonal antibody technique) in different v ascular beds leg, lung, small intestine, and spleen) were monitored in wild-type (C57BL) and ICAM-1-deficient mice, before and after adminis tration of tumor necrosis factor (TNF)-alpha. In wild-type mice, TNF-a lpha elicited time-dependent increases in lung and intestine mICAM-1 ( plateau achieved at 12 hours), with a corresponding increase in plasma sICAM-1 (Peak:ed at 5 hours and then declined), The initial increases in mICAM-1 and pulmonary leukocyte sequestration (measured as lung my eloperoxidase activity) induced by TNF-alpha preceded any detectable e levation iii slCAM-1, In ICAM-1-deficient mice, plasma sICAM-1 was red uced by similar to 70%, with >95% reductions of mICAM-1 in lung and in testine, and >75% reduction in splenic accumulation of anti-ICAM-1 ant ibody, Although TNF-alpha doubled plasma sICAM-1 in ICAM-1-deficient m ice, mICAM-1 was unaffected in all tissues, Either splenectomy or pret reatment with cycloheximide resulted in an attenuated TNF-induced incr ease in sICAM-1, without affecting mICAM-1 expression. These findings indicate that plasma sICAM-1 concentration does not accurately, reflec t the level of ICAM-1 expression on endothelial cells in different vas cular beds.