High doses of intravenous immunoglobulin G enhance Kupffer cell phagocytic function during the late phase of sepsis and endotoxemia in rats.
The effect of intravenous immunoglobuln G (ivIG) on the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia in rats was studied by using in vivo microscopy. One hour after administration of a clinically relevant dose of ivIG (0.5 g/kg body weight, Sandoglobulin), rats were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP) or were injected intravenously with lipopolysaccharide (LPS, 0.1 mg/kg body weight). Twenty-four hours after CLP or LPS, the number of leukocytes adhering to the sinusoidal wall was increased 11.0-fold in CLP-treated animals and 5.6-fold in LPS-treated animals, respectively, compared with the controls. Concomitantly, the numbers of swollen sinusoidal endothelial cells were increased 4.2-fold and 3.2-fold. The number of perfused sinusoids was decreased by 35% and by 24%. These responses were minimized by pretreatment with high doses of ivIG. Kupffer cell phagocytic activity in the periportal sinusoids in CLP-treated animals was decreased by 41%, whereas that in the centrilobular sinusoids in LPS-treated animals was increased by 72%. IvIG significantly elevated this activity in both CLP- and LPS-treated animals and the number of ED2-positive Kupffer cells in tissue sections. The results suggest that ivIG limits the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia by affecting Kupffer cell function.
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Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson 85724-5044, USA.
Lukita-Atmadja
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Machen
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Baker
G L
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McCuskey
R S
RS
D000818:Animals; D002448:Cell Adhesion; D004727:Endothelium / Q000473:pathology; D019446:Endotoxemia / Q000276:immunology / Q000628:therapy*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007416:Intestinal Perforation / Q000150:complications; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D009504:Neutrophils / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000628:therapy*
D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides