CD44 triggering enhances human NK cell cytotoxic functions

Ricciarda Galandrini, Ruggero De Maria, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

CD44, a major hyaluronate receptor, is involved in a variety of lymphocyte functions including lympho-hemopoiesis, adhesion to high endothelial venules or the extracellular matrix, and T cell activation. Here we investigated the ability of CD44 to affect the cytotoxic functions of human NK cells. Ligation of CD44 by selected mAb (J173 and F10442) resulted in a rapid, dose- response-dependent enhancement of NK cytotoxic activity against a panel of tumor target cells that varied in their sensitivity to NK killing. Neither enhanced killing against NK-resistant target cells nor CD44 mAb-mediated redirected lysis was not observed. CD44 cross-linking also was found to up- regulate CD16-mediated lysis. In an attempt to investigate the early biochemical events that occur after CD44 ligation, we found that optimal cross-linking conditions induce a rapid increase of intracellular free calcium levels, which is abrogated by extracellular Ca2+ chelation. Moreover, enhanced and more sustained Ca2+ rise resulted from CD16 and CD44 coengagement. In contrast, no inositol 1,4,5-trisphosphate generation was found after optimal CD44 cross-linking. These results suggest that although CD44 is not capable of delivering a lytic signal in human NK cells, it coactivates spontaneous or CD16-mediated NK cytotoxicity. The variation in intracellular free calcium may be one of the signals that account for the costimulation of the lytic activity.

Original languageEnglish
Pages (from-to)4399-4407
Number of pages9
JournalJournal of Immunology
Volume153
Issue number10
Publication statusPublished - Nov 15 1994

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Natural Killer Cells
Ligation
Calcium
Inositol 1,4,5-Trisphosphate
Venules
Extracellular Matrix
Up-Regulation
Lymphocytes
T-Lymphocytes
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Galandrini, R., De Maria, R., Piccoli, M., Frati, L., & Santoni, A. (1994). CD44 triggering enhances human NK cell cytotoxic functions. Journal of Immunology, 153(10), 4399-4407.

CD44 triggering enhances human NK cell cytotoxic functions. / Galandrini, Ricciarda; De Maria, Ruggero; Piccoli, Mario; Frati, Luigi; Santoni, Angela.

In: Journal of Immunology, Vol. 153, No. 10, 15.11.1994, p. 4399-4407.

Research output: Contribution to journalArticle

Galandrini, R, De Maria, R, Piccoli, M, Frati, L & Santoni, A 1994, 'CD44 triggering enhances human NK cell cytotoxic functions', Journal of Immunology, vol. 153, no. 10, pp. 4399-4407.
Galandrini R, De Maria R, Piccoli M, Frati L, Santoni A. CD44 triggering enhances human NK cell cytotoxic functions. Journal of Immunology. 1994 Nov 15;153(10):4399-4407.
Galandrini, Ricciarda ; De Maria, Ruggero ; Piccoli, Mario ; Frati, Luigi ; Santoni, Angela. / CD44 triggering enhances human NK cell cytotoxic functions. In: Journal of Immunology. 1994 ; Vol. 153, No. 10. pp. 4399-4407.
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