IntroductionNatural killer (NK) cells constitute approximately 10% to 15% of the total blood lymphocytes, and are defined by the absence of CD3 and presence of CD56 on their surface. 1 Based on the expression of CD56 and CD16, they can be divided into 2 subsets: CD56 dim CD16 hi and CD56 bright CD16 lo/Ϫ . 2,3 In peripheral blood, CD56 dim cells constitute 90% of the total NK cells. They are potent killers and are capable of destroying virus-infected cells and tumor cells without prior sensitization. In contrast, the cytotoxic potential of CD56 bright cells is limited, but they are known to produce large amounts of cytokines and chemokines such as interferon ␥ (IFN␥), tumor necrosis factor ␣ (TNF␣), macrophage inflammatory proteins (MIPs) MIP-1␣ and MIP-1, and granulocyte-macrophage colonystimulating factor (GM-CSF), which in turn can recruit other immune cells and exhibit immunomodulatory effects on their functional activities. [4][5][6] Polymorphonuclear cells (PMNs) phagocytose either directly or via various receptors (such as Fc receptors, complement receptors, and others) and subsequently kill pathogens by producing enzymes, such as defensins, proteases, permeability inducing factors, and toxic reactive oxygen and nitrogen species. 7-9 They have a short half-life of 6 to 8 hours in circulation. Senescent PMNs and PMNs that have accomplished their task of killing invading microorganisms undergo apoptosis to prevent the release of toxic components into the surroundings that would damage the host tissue. 10 However, removal of PMNs implies a reduction in the ability of the first line of defense to quickly eliminate pathogens. Various inflammatory cytokines such as interleukin-1 (IL-1), IL-2, TNF␣, IL-15, IFN␥, granulocyte-colony stimulating factor (G-CSF), GM-CSF, IL-6, and IL-8, and other mediators like lipopolysaccharide (LPS) have been shown to enhance PMN survival. 10 NK cells are known to have immunoregulatory effects on immune cells, such as T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. [11][12][13][14] Previous in vitro studies in human and murine models have addressed the effects of PMNs on NK-cell functions. [15][16][17][18] However, to our knowledge, the impact of NK cells on PMNs has not been studied. Because NK cells and PMNs are among the first cells to be recruited to the site of inflammation, reciprocal interaction between them is highly plausible. In this study, we investigated the impact of NK cells on PMN survival, activation, and function. We show that soluble factors released by cytokine-activated NK cells send survival signals to PMNs, which may promote their accumulation for extended time periods at the site of inflammation and support their functions.
Methods
Cell isolation and culturePeripheral blood mononuclear cells (PBMCs) were separated from blood filters obtained from the Institute of Transfusion Medicine, Hannover Medical School, by Ficoll density gradient centrifugation (Biochrom). PBMCs were stained...
