Disease relevance of choline phosphate

• Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae [1].
• Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract [2].
• The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl [3].
• Elicitation of delayed-type hypersensitivity to phosphorylcholine by monoclonal anti-idiotypic antibodies in an allogeneic environment [4].
• Studies with another monoclonal IgA antibody-containing antigen-binding activity to phosphorylcholine also demonstrated the ability of IgA antibody to cause acute lung injury in the rat [5].

Psychiatry related information on choline phosphate

• In addition, the binding of labeled MOPC-167 to anti-A48 Id antibodies was not inhibited by PC but was inhibited by A48 and 3-76-42 MAb bearing A48, UPC-10 non-antigen-inhibitable idiotopes [6].
• At early stages of Alzheimer's disease, phosphomonoesters (PMEs) including phosphocholine (P-choline) are present at elevated levels [7].
• Six patients with vascular dementia had lower choline and elevated phosphocholine levels, when compared to controls, but normal levels of GPCh [8].
• The new procedure, which used p-toulenesulfonate instead of 2-bromoethyl phosphorylcholine, not only reduced the reaction time but also allowed the reaction to proceed under mild conditions [9].

High impact information on choline phosphate

• We constructed chimeric receptor chains in which an immunoglobulin heavy chain variable region (VH) from a phosphorylcholine-specific antibody is substituted for T cell receptor (Tcr) alpha and beta V regions [10].
• Amino acid sequence analyses of heavy-chain variable (VH) regions from 19 myeloma and hybridoma immunoglobulins binding phosphorylcholine show that 10 are identical (the prototype T15 VH sequence) and 9 are distinct variants differing by one to eight residues [11].
• Attachment of the bacterial phosphorylcholine to the PAF receptor enhanced adherence, which was coupled to invasion of endothelial, epithelial and PAF-receptor-transfected cells [12].
• Phosphorylcholine acts as a Ca2+-dependent receptor molecule for lymphocyte perforin [13].
• The amino-acid sequence Phe-Tyr-Met-Glu is unique to phosphorylcholine (PC)-binding antibodies [14].

Chemical compound and disease context of choline phosphate

• The results of these studies document that, during anaphylaxis in the isolated guinea pig heart, a platelet-activating factor is released into the coronary effluent that has physicochemical and functional properties similar to those of acetyl glyceryl ether phosphorylcholine [15].
• The magnetic resonance spectroscopy data indicated that elevated phosphocholine in breast cancer cells was primarily attributable to increased choline kinase activity and increased catabolism mediated by increased phospholipase C activity [16].
• In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT) [17].
• Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells [18].
• Splenocytes from DBA/2 mice inoculated 3 wk earlier with syngeneic P815 mastocytoma tumor cells produce increased numbers of antibody plaque-forming cells (PFC) when stimulated with either sheep red blood cells (SRBC) or phosphorylcholine (PC) on Streptococcus pneumoniae R36a in vitro [19].

Biological context of choline phosphate

• These experiments showed that the affinity constant of the Fv fragment is identical to that of the native antibody McPC603, that there is one binding site for phosphorylcholine in the Fv fragment, and that there is no inactive protein in the preparation [20].
• The variable domains of the phosphorylcholine-binding antibody McPC603 were secreted together into the periplasmic space, where protein folding as well as heterodimer association occurred correctly [20].
• Phosphorylcholine-specific helper T cells in mice with an X-linked defect of antibody production to the same hapten [21].
• Furthermore, IL-4R is not coupled to sphingomyelinase (SMase) since IL-4, unlike exogenous SMase, did not generate ceramide but induced the hydrolysis of PC to pchol that was comparable to exogenous PLC [22].
• Hybridomas were established from splenic B cells of mice carrying two copies of the TCR transgene after hyperimmunization with phosphorylcholine keyhole limpet hemocyanin [23].

Anatomical context of choline phosphate

• Phosphorylcholine (PC) is found as part of lecithin and sphingomyelin molecules in variable amounts in eukaryotic and prokaryotic membranes, including plasma membranes [24].
• There seem to be more VH regions participating in the phosphorylcholine response than can be encoded directly by germ-line VH gene segments [25].
• Expression of phosphorylcholine-specific B cells during murine development [26].
• 17 hybridomas produced antibody that bound intact R36A and did not cross-react with phosphocholine, an antigen common in the cell wall of all S. pneumoniae [27].
• We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines [28].

Associations of choline phosphate with other chemical compounds

• Reconstitution with a monoclonal IgM specific to phosphatidylcholine, a conserved cell membrane component, has a modest effect but a monoclonal IgM specific to phosphocholine is not protective [29].
• We have examined the ontogeny of BALB/c plaque-forming cell (PFC) responses to phosphorylcholine (PC) from fetal and neonatal liver by using the (CBA/N x BALB/c)F1 transplantation model [30].
• The cell wall polysaccharide (PnC) extracted from Pn was used to form complexes with TEPC-15, a myeloma protein that binds to phosphorylcholine determinants on the PnC [31].
• The main step in PCho biosynthesis in Arabidopsis thaliana is the triple, sequential N-methylation of phosphoethanolamine, catalyzed by S-adenosyl-l-methionine:phosphoethanolamine N-methyltransferase (PEAMT) [32].
• Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin [33].
• We show that a protein limited in its distribution to pathogenic Neisseria species and structurally related to enzymes implicated in phosphoethanolamine modification of lipopolysaccharide is necessary for PilE covalent modification with phosphoethanolamine and phosphocholine [34].

Gene context of choline phosphate

• Neutral sphingomyelinases sphingomyelin phosphodiesterase (SMPD)2 and -3 hydrolyze sphingomyelin to phosphocholine and ceramide. smpd2 is expressed ubiquitously, and smpd3 is expressed predominantly in neurons of the CNS [35].
• In contrast, the lower concentration of 10 micromol/L U0126 for 40 hours had no significant effect on either P-ERK1/ 2 or phosphocholine levels in MDA-MB-231 cells [36].
• Thus, phosphocholine has potential as a noninvasive pharmacodynamic marker for monitoring MAPK signaling blockade [36].
• C-reactive protein (CRP), the major human acute-phase plasma protein, binds to phosphocholine (PCh) residues present in pneumococcal C-polysaccharide (PnC) of Streptococcus pneumoniae and to PCh exposed on damaged and apoptotic cells [37].
• Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62 [38].

Analytical, diagnostic and therapeutic context of choline phosphate

• An amino acid sequence analysis of the N-terminal immunoglobulin heavy and light chain variable regions (VH and VL) from 16 hybridoma proteins which bind phosphorylcholine as well as the complete sequence analysis of 9 of these VH regions is presented [25].
• The CMP-5' parts of the molecules in the crystal structure are strongly linked by metal ligation and hydrogen bonds leaving the phosphoryl-choline residues relatively free [39].
• Of these, only MOPC-167, an IgAk phosphocholine (PC)-binding myeloma protein, gave a significant inhibition of binding of labeled A48 to anti-A48 Id antibodies by radioimmunoassay and enzyme-linked immunosorbent assay [6].
• Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance [40].
• Mice treated in this way lacked peritoneal-resident Ly-1 B cells, contained greatly reduced serum immunoglobulin M levels, and were unable to generate significant in vivo antibody responses to intraperitoneal injections of alpha 1,3-dextran or phosphorylcholine, antigens for which specific B cells reside in the Ly-1 B cell subset [41].

References