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PMID: 16203869 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells.

The Journal of experimental medicine ·Vol. 202 ·No. 7 ·2005-10-03 ·Pages 1001-12

Bryceson YT, March ME, Barber DF, Ljunggren HG, Long EO

Abstract

The relative contribution to cytotoxicity of each of the multiple NK cell activation receptors has been difficult to assess. Using Drosophila insect cells, which express ligands of human NK cell receptors, we show that target cell lysis by resting NK cells is controlled by different receptor signals for cytolytic granule polarization and degranulation. Intercellular adhesion molecule (ICAM)-1 on insect cells was sufficient to induce polarization of granules, but not degranulation, in resting NK cells. Conversely, engagement of the Fc receptor CD16 by rabbit IgG on insect cells induced degranulation without specific polarization. Lysis by resting NK cells occurred when polarization and degranulation were induced by the combined presence of ICAM-1 and IgG on insect cells. Engagement of receptor 2B4 by CD48 on insect cells induced weak polarization and no degranulation. However, coengagement of 2B4 and CD16 by their respective ligands resulted in granule polarization and cytotoxicity in the absence of leukocyte functional antigen-1-mediated adhesion to target cells. These data show that cytotoxicity by resting NK cells is controlled tightly by separate or cooperative signals from different receptors for granule polarization and degranulation.

MeSH Terms
Animals Antigens, CD/metabolism Cell Adhesion/immunology Cells, Cultured Cloning, Molecular Cytoplasmic Granules/metabolism Cytotoxicity Tests, Immunologic Cytotoxicity, Immunologic/immunology DNA Primers Drosophila Enzyme-Linked Immunosorbent Assay Humans Intercellular Adhesion Molecule-1/genetics,metabolism Killer Cells, Natural/metabolism Membrane Glycoproteins/metabolism Receptors, IgG/metabolism Receptors, Immunologic/metabolism Signal Transduction/immunology Signaling Lymphocytic Activation Molecule Family
Chemicals
Antigens, CD CD244 protein, human DNA Primers Membrane Glycoproteins Receptors, IgG Receptors, Immunologic Signaling Lymphocytic Activation Molecule Family Intercellular Adhesion Molecule-1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bryceson Yenan T
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
March Michael E
Barber Domingo F
Ljunggren Hans-Gustaf
Long Eric O
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20051143
Published
2005-10-03
Pages
1001-12
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213171
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1084/jem.20051143 PMC Full Text View journal details
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