Enhancement of lymphokine-activated killer cell activity by fibronectin.
In this study, we demonstrated that immobilized fibronectin (FN) enhanced lymphokine-activated killer cell (LAK) activity, and that the enhanced LAK activity was completely abrogated by an anti-VLA-5 monoclonal antibody and RGD peptide. Fresh spleen cells expressed VLA-4, VLA-6, and vitronectin receptor, whereas VLA-5 was expressed only on the spleen cells activated with interleukin-2. LAK cells showed increased adhesion to immobilized FN compared with that to control bovine serum albumin, and the increased adhesion of LAK cells to immobilized FN was inhibited by anti-VLA-5 monoclonal antibody. Conjugate-formation assay showed that the LAK cells cultured on immobilized FN bound to target cells more efficiently than the control LAK cells, and that anti-LFA-1 monoclonal antibody inhibited the LAK-target cell binding. Immobilized type IV collagen and laminin, as well as FN, enhanced LAK activity. All of these results suggest that the interaction of integrins expressed on LAK cells with extracellular matrix proteins acts in a costimulatory manner for the enhancement of LAK activity, and that anchorage is necessary for full activation of LAK cells.
Li
Y Q
YQ
Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Kobayashi
M
M
Kuramitsu
Y
Y
Yuan
L
L
Matsushita
K
K
Yagita
H
H
Okumura
K
K
Hosokawa
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology*; D016130:Immunophenotyping; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016169:Lymphocyte Function-Associated Antigen-1; D009842:Oligopeptides; D017469:Receptors, Fibronectin; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline