Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells

Maghazachi, Azzam A.

doi:10.1124/pr.57.3.5

Cited by 42 publications

(54 citation statements)

References 178 publications

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“…Functionally, these cells are important in immune responses to viral infections as well as controlling tumor growths [85,86] . The activities of these cells are regulated by activating and inhibitory receptors, which by intracellular integration of challenges and inhibitions determine the cell course of action [87] . NK cells recognize and are activated by cells that are in distress by detecting stress induced ligands on target cells through natural cytotoxicity receptors, such as NKp30, NKp44, or NKp46, and the C-type lectin receptor NKG2D, among others [87,88] .…”

Section: Role Of B Cellsmentioning

confidence: 99%

“…The activities of these cells are regulated by activating and inhibitory receptors, which by intracellular integration of challenges and inhibitions determine the cell course of action [87] . NK cells recognize and are activated by cells that are in distress by detecting stress induced ligands on target cells through natural cytotoxicity receptors, such as NKp30, NKp44, or NKp46, and the C-type lectin receptor NKG2D, among others [87,88] . In healthy cells however, activating factors are held in equilibrium by inhibiting signals.…”

Section: Role Of B Cellsmentioning

confidence: 99%

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Multiple sclerosis and the role of immune cells

Høglund

Maghazachi

2014

WJEM

131

101

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Multiple sclerosis (MS) is a complex disease with many different immune cells involved in its pathogenesis, and in particular T cells as the most recognized cell type. Recently, the innate immune system has also been researched for its effect on the disease. Hence, cells of the immune system play vital roles in either ameliorating or exacerbating the disease. The genetic and environmental factors, as well as the etiology and pathogenesis are of utmost importance for the development of MS. An insight into the roles play by T cells, B cells, natural killer cells, and dendritic cells in MS and the animal model experimental autoimmune encephalomyelitis, will be presented. Understanding the mechanisms of action for current therapeutic modalities should help developing new therapeutic tools to treat this disease and other autoimmune diseases.

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Section: Role Of B Cellsmentioning

confidence: 99%

Section: Role Of B Cellsmentioning

confidence: 99%

Multiple sclerosis and the role of immune cells

Høglund

Maghazachi

2014

WJEM

131

101

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“…5,6 The activities of NK cells are regulated through activating and inhibiting receptors, which determine the course of action of these cells. 7 NK cells are activated through distress via the detection of stress-induced ligands on target cells by NK cytotoxicity receptors, which include NKp30, NKp44, NKp46 and C-type lectin receptors, such as NKG2D. 8 In addition, NK cells express several receptors that inhibit activation, including killer cell immunoglobulin-like receptors, which interact with HLA-I molecules, and CD94-NKG2A, which interacts with HLA-E.…”

Section: Introductionmentioning

confidence: 99%

Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CD107a

et al. 2014

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Dimethyl fumarate (DMF) is a new drug used to treat multiple sclerosis (MS) patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate (MMF) on various activities of natural killer (NK) cells. We demonstrated that MMF augments the primary CD56 1 , but not CD56 2 , NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56 1 , but not CD56 2 , NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56 1 NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56 1 NK cells. Thus, these results are the first to show that MMF augments CD56 1 NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.

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“…The FPR2 ligand includes host-derived agonists (LL-37, lipoxin A 4 , and serum amyloid A) and synthetic peptides (WKYMVm and MMK-1) (14 -18). Moreover, the FPR3 ligand includes Helicobacter pylori-derived Hp [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] (19), the heme-binding protein cleavage product F2L (Ac-ML GMIKNSLFGSVETWPWQVL) (20), and a synthetic peptide (WKYMVm) (21). Members of the FPR family play an important immunologic function, including host defense against pathogens via the modulation of chemotactic migration and superoxide generation in human monocytes, as well as in neutrophils (8,9).…”

mentioning

confidence: 99%

Functional Expression of Formyl Peptide Receptor Family in Human NK Cells

Kim

et al. 2009

The Journal of Immunology

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We determined the expression of the formyl peptide receptor (FPR) family and the functional roles of the FPR family in NK cells. All tested human NK cells express two members of the FPR family (FPR1 and FPR2). The expression of FPR3 was noted to occur in a donor-specific manner. The stimulation of NK cells with FPR family-selective agonists (fMLF (N-formyl-Met-Leu-Phe), MMK-1, F2L, and WKYMVm (Trp-Lys-Tyr-Met-Val-d-Met)) elicited cytolytic activity in resting NK cells, but not in IL-2-activated NK cells; the cytolytic activity was not inhibited by pertussis toxin. The FPR family agonists also stimulated chemotactic migration of IL-2-activated NK cells, but not resting NK cells; the chemotactic migration was completely inhibited by pertussis toxin. WKYMVm stimulates ERK, p38 MAPK, and JNK activities in both resting and IL-2-activated NK cells. WKYMVm-induced chemotactic migration was partially inhibited by PD98059 (2′-amino-3′-methoxyflavone); however, the inhibition of JNK by its selective inhibitor (SP600125, anthra[1,9-cd]pyrazol-6(2H)-one) dramatically inhibited the WKYMVm-induced cytolytic activity. Furthermore, WKYMVm-induced chemotactic migration and cytolytic activity were partly inhibited by FPR family-selective antagonists (cyclosporin H and WRWWWW). Taken together, our findings indicate that human NK cells express functional members of the FPR family, and in turn the activation of the three members of the FPR receptor family elicit cytolytic activity in NK cells, thus suggesting that the receptors are potentially important therapeutic targets for the modulation of NK cell-mediated immune responses.

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Insights into Seven and Single Transmembrane-Spanning Domain Receptors and Their Signaling Pathways in Human Natural Killer Cells

Cited by 42 publications

References 178 publications

Multiple sclerosis and the role of immune cells

Multiple sclerosis and the role of immune cells

Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CD107a

Functional Expression of Formyl Peptide Receptor Family in Human NK Cells

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