Disease relevance of CD160

• To determine whether susceptibility to the common (CD10+) form of childhood ALL (c-ALL) is associated with NK1 or NK2, we carried out a molecular analysis of 94 childhood c-ALL patients and 136 infant controls [1].
• The compound CP 96345 is a high-affinity, non-peptide antagonist of the substance P (NK1) receptor, which is important in pain perception and neurogenic inflammation [2].
• Expression of these mutants causes a COS cell NK1 clone to undergo pertussis toxin-sensitive apoptosis in an FAD trait-linked manner by activating the G protein Go, which consists of G alpha(o) and G betagamma subunits [3].
• Activation of protein kinase C (PKC) was achieved either directly by treatment with 4-alpha-phorbol 12-myristate 13-acetate (PMA) or by activating the Galpha(q)-coupled human substance P receptor (hNK-1) co-expressed with hDAT in HEK293 cells and in N2A neuroblastoma cells [4].
• The reduction in postoperative pain at doses not producing side effects suggests that NK1 antagonists may be clinically useful [5].

Psychiatry related information on CD160

• Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia [6].
• METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions [7].
• Phase-advances of locomotor activity rhythm that can normally be induced by light pulses given during the late subjective night were markedly reduced by pre-treatment with the NK1 antagonist [8].
• Sparing of striatal neurons coexpressing calretinin and substance P (NK1) receptor in Huntington's disease [9].
• Anxiolytic actions of the substance P (NK1) receptor antagonist L-760735 and the 5-HT1A agonist 8-OH-DPAT in the social interaction test in gerbils [10].

High impact information on CD160

• We present data confirming that the NK1 specificity depended on Lys80 (and not on Asn77); however recognition of NK2 ligands by NK cells was also controlled by the amino acid at position 80 (Asn), and mutation of Ser77 had no effect [11].
• It has been reported that protection from NK1 killers depended on the presence of the Lys residue at position 80, an upward pointing residue near the end of the alpha 1 helix (and not on Asn77), whereas inhibition of NK2 effector cells required Ser77, a residue deep in the F pocket and interacting with the peptide (and not Asn80) [11].
• Autoradiographic ligand binding to human umbilical cord sections demonstrates the presence of SP binding sites with characteristics of the neurokinin 1 (NK-1) receptor (displacement by GTP analogues and the NK-1 specific antagonist CP-96,345) on human umbilical arterial, but not venous, endothelium [12].
• We investigated which subunit was responsible for the induction of apoptosis by V642I APP in NK1 cells [3].
• Compared with normal mammary epithelial cells (n = 2) and benign breast biopsies (n = 21), BC cell lines (n = 7) and malignant breast biopsies (n = 25) showed increased expression of PPT-I and NK-1 [13].

Chemical compound and disease context of CD160

• The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333, on the functional consequences of NK1 receptor activation in a human astrocytoma cell line, U373MG, were investigated [14].
• S-100 and NK1/C3 were the most sensitive stains for detecting metastatic melanoma; however, they both also stain other nontumor cells in lymph nodes [15].
• The action of the NK1 tachykinin receptor antagonist, CP 99,994, in antagonizing the acute and delayed emesis induced by cisplatin in the ferret [16].
• The effects of a NK1 antagonist, GR205171, and a 5-HT3 antagonist, ondansetron, in a novel model of post-anaesthesia-induced emesis in Suncus murinus is described [17].
• PURPOSE: Aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist approved for the treatment and prevention of emesis caused by moderately and highly emetogenic chemotherapy, is an inhibitor, inducer, and substrate of the cytochrome P450 3194 pathway [18].

Biological context of CD160

• BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression [19].
• We had previously reported, using BY55 monoclonal antibody, a cell surface 80-kDa protein restricted to human functional peripheral blood cytotoxic lymphocytes with either natural killer CD3- or cytotoxic T lymphocyte CD3+CD8+ phenotype [20].
• We also demonstrated that sHLA-G1 induces endothelial cell apoptosis through binding to BY55/CD160, a glycosylphosphatidylinositolanchored receptor expressed by endothelial cells [21].
• We further found that CD160 engagement induced marked phosphorylation of Akt, as evidenced by western blotting [22].
• Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides [13].

Anatomical context of CD160

• Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement [23].
• CD160 is expressed by most intestinal intraepithelial lymphocytes and by a minor subset of circulating lymphocytes including NK, TCRgammadelta and cytotoxic effector CD8bright+CD28- T lymphocytes [19].
• Our results showed that BY55 mAb labeled only 5-10% of the bone marrow lymphocytes, which included a major proportion of CD3+ CD8+ cytotoxic T lymphocytes [20].
• Furthermore, we detected in cord blood no cytotoxic T lymphocyte activity but we demonstrated that the CD3-BY55+ cell subset contained the whole natural killer activity [20].
• In human tissues, BY55 mRNA was expressed only in spleen, PBL, and small intestine (in gut lymphocytes) [24].

Associations of CD160 with chemical compounds

• Further, we found that CD160 co-precipitates with the protein tyrosine kinase p56lck and tyrosine phosphorylated zeta chains upon TCR-CD3 cell activation [19].
• BY55 was expressed on all intestinal intraepithelial lymphocytes, which were predominantly CD3+TCRalpha/beta+CD4-CD8+CD11b+CD28-CD45RO+C D56-CD101+CD103+ (alphaEbeta7 integrin) [24].
• This chimeric exchange, corresponding to 17 nonconserved residues, conveyed full susceptibility for the NK2-specific compound SR-48,968 to the previously unresponsive NK1 receptor--i.e., the Ki value for inhibition of binding of 125I-labeled substance P decreased from > 10,000 to 0.97 nM [25].
• Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors [26].
• Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy [27].

Physical interactions of CD160

• In this study, we further report that short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form through a proteolytic cleavage involving a metalloprotease [28].

Regulatory relationships of CD160

• CD160 is an Ig-like activating NK cell receptor expressed on the majority of circulating NK cells [29].
• In addition, we demonstrate that CD160 mRNA synthesis can be induced in CD56(bright) separated lymphocytes following exposure to IL-15 [28].

Other interactions of CD160

• This unique CD160-mediated cytokine production differs from the one observed after CD16 engagement whose expression is also restricted to the CD56dim cytotoxic NK cell subset [29].
• As already reported for the CD160-mediated cytotoxic effector function, CD160-mediated cytokine production by peripheral blood-NK cells is negatively controlled by the killer Ig-like receptor CD158b [29].
• HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells [30].
• We also observed that CD160 surface expression on NK cells is down-modulated upon activation with PMA or IL-2 [28].
• Novel markers were demonstrated to correlate with CTL properties, such as the 2B4 (CD244) receptor, a member of the CD2 subset of the immunoglobulin superfamily or the glycosylphosphatidylinositol-anchored CD160 receptor [31].

Analytical, diagnostic and therapeutic context of CD160

• First, we observed by confocal microscopy that engagement of CD160 induces its polarization and co-localization with PI3K [22].
• How CD160 intracellular signaling is mediated following its specific ligation is unknown [32].
• In this study, we investigated a role for PPT-I and its receptors, neurokinin-1 (NK-1) and NK-2, in BC by using quantitative reverse transcription-PCR, ELISA, and in situ hybridization [13].
• Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1 [33].
• The interactions of hepatocyte growth factor/scatter factor and its NK1 and NK2 variants with glycosaminoglycans using a modified gel mobility shift assay. Elucidation of the minimal size of binding and activatory oligosaccharides [34].

References