TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma.
Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions.
Pilaro
A M
AM
Laboratory of Experimental Immunology, PRI/DynCorp, NCI-FCRDC, Frederick, MD 21702.
Taub
D D
DD
McCormick
K L
KL
Williams
H M
HM
Sayers
T J
TJ
Fogler
W E
WE
Wiltrout
R H
RH
D000818:Animals; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D008099:Liver / Q000166:cytology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha