NDLI: Tyrosine kinase activation in LPS stimulated rat kupffer cells

Content Provider	Springer Nature Link
Author	Schultze, Bobert L. Gangopadhyay, Aniruddha Cay, Osman Lazure, Donald Thomas, Peter
Copyright Year	1999
Abstract	Kupffer cells, a majority of the body's fixed macrophages, are a major site of bacterial lipopolysaccharide (LPS) metabolism and are mediators in the body's response to sepsis. Uptake of LPS is different in Kupffer cells than other macrophages. Signal transduction in other macrophages in response to LPS involves phosphorylation of proteins in the 50–60 kDa range. We hypothesized that Kupffer cells may have unique signal transduction pathways in response to LPS. Rat Kupffer cells were exposed to LPS (1 μg/mL) for varying times ranging from 15 to 90 min. Cell lysates were Western blotted using an anti-phosphotyrosine antibody. The blots showed an increase in the amount of tyrosine phosphorylation on two proteins of 119 kDa and 83 kDa. The effects of varying LPS concentration (1 ng/mL-1 μg/mL) showed an increasing amount of phosphorylation with increasing LPS concentration. To associate the importance of tyrosine phosphorylation in the response of Kupffer cells to LPS, the tyrosine kinase inhibitors, tyrphostin, lavendustin, and genisten were used to study the effects of inhibiting phosphorylation on TNF-α production. Kupffer cells were preincubated in the presence of the inhibitor and exposed to LPS (1 μg/mL). TNF-α was measured in the conditioned media by ELISA. A 70% or greater decrease in TNF-α production was observed. When phagocytosis of latex beads by rat Kupffer cells was measured in vivo using intravital video microscopy, LPS treatment significantly increased uptake. This increase in phagocytosis was inhibited by tyrphostin. These results show what may be unique phosphorylation events in Kupffer cells that are related to LPS induced production of TNF-α.
Starting Page	287
Ending Page	301
Page Count	15
File Format	PDF
ISSN	10859195
Journal	Cell Biochemistry and Biophysics
Volume Number	30
Issue Number	2
e-ISSN	15590283
Language	English
Publisher	Humana Press
Publisher Date	1999-01-01
Publisher Place	Totowa
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biochemistry Pharmacology/Toxicology Biotechnology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Biochemistry Biophysics

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