Cytokine-activated NK cells inhibit PMN apoptosis and preserve their functional capacity.
Natural killer (NK) cells and polymorphonuclear cells (PMNs) play a critical role in the first line of defense against microorganisms. Upon host infection, PMNs phagocytose invading pathogens with subsequent killing by oxidative or nonoxidative mechanisms. NK cells are known to have immunoregulatory effects on T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. However, their impact on PMN survival and function is not well known. We found that soluble factors derived from cytokine-activated NK cells delay PMN apoptosis and preserve their ability to perform phagocytosis and produce reactive oxygen species (ROS). The expression patterns of CD11b and CD62L on PMNs differed according to the cytokine combination used for NK-cell stimulation. Irrespective of the NK-cell treatment, however, PMN survival was prolonged with sustained functional capacity. We found that interferon gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha produced by NK cells upon stimulation with cytokines played a crucial role in NK cell-mediated effects on PMNs. Our study demonstrates that soluble factors derived from cytokine-activated NK cells send survival signals to PMNs, which would promote their accumulation and function at the site of inflammation in vivo.
Bhatnagar
Nupur
N
Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
Hong
Henoch S
HS
Krishnaswamy
Jayendra K
JK
Haghikia
Arash
A
Behrens
Georg M
GM
Schmidt
Reinhold E
RE
Jacobs
Roland
R
D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019002:CD56 Antigen; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology / Q000473:pathology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism
D015415:Biomarkers; D019002:CD56 Antigen; D016207:Cytokines; D017382:Reactive Oxygen Species