Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats.
Cell adhesion molecules are important for localized accumulation of phagocytes at sites of tissue damage. In the present studies, we analyzed the effects of blocking hepatic macrophages on expression of beta2 integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cells during acute endotoxemia. Flow cytometric analysis revealed distinct subpopulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intravenously) resulted in a time-dependent increase in the percentage of small, dense macrophages and a progressive loss of larger, less-dense cells. In contrast, no major effects were observed on the physical properties of hepatocytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages. Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expression on hepatocytes, which was observed within 3 hours and reached a maximum after 24 hours. An increase in ICAM-1 expression was also observed on endothelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expressed beta2 integrins. Induction of acute endotoxemia had no effect on beta2 integrin expression by these cells. Pretreatment of rats with gadolinium chloride (GdCl3), a macrophage inhibitor known to block endotoxin-induced liver injury, abrogated the effects of endotoxin on ICAM-1 expression by hepatocytes and macrophages. In contrast, ICAM-1 expression on endothelial cells increased. Interestingly, treatment of rats with GdCl3 alone resulted in a marked increase in expression of ICAM-1 on endothelial cells and hepatocytes, and of beta2 integrins on macrophages and endothelial cells. Taken together, these data suggest that ICAM-1 is involved in mediating macrophage adherence and accumulation in the liver during endotoxemia. Furthermore, macrophages appear to regulate expression of this cell adhesion molecule on parenchymal cells.
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854-8020, USA.
N
N
Ahmad
C R
CR
Gardner
E J
EJ
Yurkow
D L
DL
Laskin
D000208:Acute Disease; D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018821:CD18 Antigens; D018799:Intercellular Adhesion Molecule-1; D005682:Gadolinium; C038958:gadolinium chloride