Role of CD44 in the development of natural killer cells from precursors in long-term cultures of mouse bone marrow.
The role of the adhesion molecule CD44 in the development of NK cells was analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture (day 0), recombinant human IL-2 was added and 13 days later the cells generated were shown to have substantial cytotoxic activity against YAC-1 and to be enriched for NK cells, as assessed for NK-1.1 phenotype by flow cytometric analysis. Physical separation between stroma and precursors partially inhibited proliferation and, consequently, a lower number of cytotoxic cells were produced. Similar results were obtained when an anti-CD44 mAb was added together with IL-2 at day 0. The disruption of hyaluronic acid (HA), one of the ligands of CD44, by hyaluronidase or the competition for the binding of CD44 by soluble HA added with IL-2 on day 0 inhibited both proliferation and development of cytotoxicity to a greater degree than did anti-CD44. These results indicate that interaction of CD44 with HA plays an important role in the development of pre-NK cells into cytotoxic effector cells.
Delfino
D V
DV
Department of Radiation Oncology, University of Pittsburgh School of Medicine, PA 15261.
Patrene
K D
KD
DeLeo
A B
AB
DeLeo
R
R
Herberman
R B
RB
Boggs
S S
SS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D001854:Bone Marrow Cells; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D006821:Hyaluronoglucosaminidase