MATRIX METALLOPROTEINASES PRODUCED BY RAT IL-2-ACTIVATED NK CELLS

Citation
Rp. Kitson et al., MATRIX METALLOPROTEINASES PRODUCED BY RAT IL-2-ACTIVATED NK CELLS, The Journal of immunology, 160(9), 1998, pp. 4248-4253
Citations number
52
Categorie Soggetti
Immunology
Journal title
ISSN journal
00221767
Volume
160
Issue
9
Year of publication
1998
Pages
4248 - 4253
Database
ISI
SICI code
0022-1767(1998)160:9<4248:MMPBRI>2.0.ZU;2-U
Abstract
We have previously documented that adoptively transferred IL-2-activat ed NK (A-NK) cells can accumulate within cancer metastases, Electron m icroscopic studies of pulmonary metastases have revealed that adoptive ly transferred A-NK cells that accumulate within metastases bind to en dothelial cells and are able to traverse basement membranes. We have n ow extended these morphologic studies. We report that rat A-NK cells p roduce two matrix metalloproteinases: MMP-2 and MMP-9, as determined b y SDS-PAGE gelatin zymography, These activities are inhibited followin g incubation with BB-94 (batimastat), a specific inhibitor of matrix m etalloproteinases but not with 3,4-dichloroisocoumarin, an inhibitor o f neutral serine proteases, The identity of MMP-2 was confirmed by Wes tern blots using a polyclonal Ab against human MMP-9, whereas reverse transcriptase-PCR analysis of mRNA extracts of A-NK cells has confirme d the presence of MMP-9. In addition, we report for the first time tha t A-NK cells can migrate through a model basement membrane-like extrac ellular matrix, Moreover, the ability of A-NK cells to migrate through this model basement membrane was partially inhibited by BB-94; howeve r, BB-94 has no effect on A-NK cell-mediated cytotoxicity, suggesting that matrix metalloproteinases do not contribute to cytolytic function of A-NK cells. In sum, our studies show that A-NK cells employ BB-94- inhibitable matrix metalloproteinases to degrade extracellular matrice s. This suggests that matrix metalloproteinases may play a role in the accumulation of A-NK cells within cancer metastases.