Upregulation of intraepithelial lymphocyte (IEL) function in the small intestinal mucosa in sepsis.
Host defense mechanisms preventing bacterial invasion are particularly important in the gastrointestinal tract, since most gram-negative infections originate from there. Intraepithelial lymphocytes (IEL) seem to play an important role in this immune surveillance of the intestine, although their function in sepsis is not fully understood. To evaluate the characteristics of IEL in sepsis, C57BL/6 mice received a non-lethal dose of LPS and IEL were harvested at various time points thereafter. Although IEL displayed no phenotypic changes after endotoxemia, they displayed enhanced cytolytic activity and increased proliferation after LPS injection In addition, IEL from septic mice showed enhanced gamma interferon (IFN-gamma) production after LPS administration. The production of IFN-gamma may have induced the increased intestinal NOS-2 mRNA expression which was observed after endotoxemia. In conclusion, endotoxemia leads to functional activation of IEL without phenotypic changes. The activation of IEL and the subsequently increased NOS-2 expression may be important mechanisms in maintaining the mucosal barrier after sublethal LPS challenge.
Nüssler
N C
NC
Department of Surgery, Charité Campus Virchow-Klinikum, Humboldt University Berlin, Germany. natascha.nuessler@charite.de
Stange
B
B
Nussler
A K
AK
Settmacher
U
U
Langrehr
J M
JM
Neuhaus
P
P
Hoffman
R A
RA
D000818:Animals; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D019446:Endotoxemia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse