NDLI: Impaired NK cytolytic activity and enhanced tumor growth in NK lytic-associated molecule-deficient mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hoover, Richard G. Kornbluth, Jacki Gullickson, Gail
Description	Country affiliation: United States Author Affiliation: Hoover RG ( Department of Veterans Affairs Medical Center, St. Louis, MO 63106, USA.)
Abstract	NK lytic-associated molecule (NKLAM) is a protein involved in the cytolytic function of NK cells. It is weakly expressed in resting NK cells but upon target cell stimulation or after incubation with cytokines that enhance NK killing, NKLAM mRNA levels increase and protein is synthesized and is targeted to cytoplasmic granule membranes. We have previously shown that NKLAM plays a role in perforin/granzyme-mediated cytolysis in vitro. To further investigate the function of NKLAM in NK cell-mediated cytotoxicity, we generated, by gene targeting, NKLAM-deficient mice. These mice have normal numbers of NK cells and other lymphoid populations in the spleen. They also have no alterations in NK maturation or NK receptor repertoire. NK cells from NKLAM-deficient and WT mice have comparable amounts of perforin, granzyme B, and lysosomal membrane-associated protein 1 (CD107a) in their cytotoxic granules and comparable levels of granule exocytosis are induced by PMA and calcium ionophore A23187. However, NKLAM-deficient NK cells display significantly less NK cytotoxic activity in vitro than WT NK cells. They also secrete less IFN-gamma upon target cell stimulation, In addition, NKLAM-deficient mice exhibit greater numbers of pulmonary metastases after i.v. injection with B16 melanoma cells. These studies indicate that NKLAM-deficient mice have diminished capacity to control tumor metastases and support the role for NKLAM in NK function both in vitro and in vivo.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cytotoxicity, Immunologic Immunology Killer Cells, Natural Membrane Proteins Neoplasms, Experimental Animals Blotting, Western Genetics Enzyme-linked Immunosorbent Assay Flow Cytometry Interferon-gamma Biosynthesis Metabolism Lymphocyte Activation Deficiency Mice Mice, Knockout Pathology Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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