Ligation of ICAM-1 molecules inhibits target cell-induced granule exocytosis of IL-12-activated natural killer cells.
The importance of cell adhesion molecules such as ICAM-1 is emphasized in cell-to-cell interactions that are critical in the generation of effective immune reactions. In this study, the involvement of ICAM-1 in natural killer (NK) cell activities was characterized in IL-12-activated human NK cells. To address the question of whether ligation of ICAM-1 molecules can modulate NK cell cytolytic activities, a 4-h (51)Cr-release assay was performed after pretreatment of NK cells with R6.5 mAb (anti-human ICAM-1 mAb). Ligation of membrane ICAM-1 molecules significantly inhibited IL-12-enhanced NK cytotoxicity against K562, and the pretreatment of neutralizing soluble ICAM-1 with R6.5 mAb blocked this inhibitory effect. The involvement of Ca(2+)-dependent granular exocytosis was evaluated. BLT esterase assay demonstrated that the ligation of ICAM-1 molecules inhibited granular exocytosis of NK cells. Additionally, the ICAM-1-mediated inhibition of Ca(2+) flux in NK cells was detected using Fluo-3AM, while the pretreatment of NK cells with R6.5 mAb did not affect conjugate formation between NK and K562 cells. Collectively, these results suggest that the signals transduced from ICAM-1 molecules might be sufficient to induce inhibitory effects on NK cells.
Cho
D H
DH
Immune Cell Signal Transduction R.U., KRIBB, Taejon, 305-600, Korea.
Song
H K
HK
Kang
H S
HS
Yoon
S R
SR
Lee
H G
HG
Pyun
K H
KH
Lee
W J
WJ
Kim
Y B
YB
Choi
I
I
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005089:Exocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D011940:Receptor Aggregation / Q000187:drug effects; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium