Kupffer cells express type I TGF-beta receptors, migrate to TGF-beta and participate in streptococcal cell wall induced hepatic granuloma formation.
Intraperitoneal injection of Group A streptococcal cell wall (SCW) fragments into female Lewis rats results in the induction of an acute hepatic inflammation that progresses to granulomatous lesions. Kupffer cells have been shown to rapidly clear circulating SCW which triggers production of TGF-beta. In this study, we examined Kupffer cells for the expression of TGF-beta receptors to determine if these cells might be modulated in an autocrine/paracrine fashion by TGF-beta during SCW-hepatic inflammation. By receptor crosslinking and subsequent SDS-PAGE analysis we demonstrate that Kupffer cells express Type I TGF-beta receptors, but not Types II and III. Scatchard analysis indicated a receptor density of approximately 1100 receptors per cell. Functionally, TGF-beta was found to be chemotactic for Kupffer cells in vitro and this chemotactic response was higher in cells isolated from rats 1-21 days post SCW-injection. Although TGF-beta 1 mRNA is constitutively expressed by Kupffer cells, in vitro stimulation of the cultures with purified TGF-beta augments the expression of TGF-beta 1 mRNA and protein synthesis suggesting autocrine/paracrine regulation. These results indicate that TGF beta secreted by Kupffer cells during SCW-induced hepatic inflammation may amplify its own expression and regulate Kupffer cell functions relevant to the formation of granulomatous lesions within the liver.
Kossmann
T
T
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Manthey
C L
CL
Brandes
M E
ME
Morganti-Kossmann
M C
MC
Ohura
K
K
Allen
J B
JB
Mergenhagen
S E
SE
Wahl
S M
SM
D000818:Animals; D002473:Cell Wall; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D015342:DNA Probes; D006099:Granuloma / Q000473:pathology / Q000503:physiopathology*; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D013290:Streptococcal Infections / Q000473:pathology / Q000503:physiopathology*; D013297:Streptococcus pyogenes; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*
D015342:DNA Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta