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PubMed2006

Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system.

During embryonic development, complex events, such as cellular proliferation, differentiation, survival, and guidance of axons, are orchestrated and regulated by a variety of extracellular signals. Receptor tyrosine kinases mediate many of these events, with several playing critical roles in neuronal survival and axonal guidance. It is evident that not all the receptor tyrosine kinases that play key roles in regulating neuronal development have been identified. In this study, we have characterized the spatial-temporal expression profile of a recently identified receptor tyrosine kinase, anaplastic lymphoma kinase (ALK), in embryonic chick by means of whole-mount in situ hybridization in conjunction with immunohistochemistry. Our findings reveal that Alk is expressed in sympathetic and dorsal root ganglia as early as stage 19. In addition, mRNA is expressed from stage 23/24 (E4) to stage 39 (E13) in discrete motor neuron subsets of chick spinal cord along with a select group of muscles that are innervated by one of these particular motor neuron clusters. Expression within the spinal cord is coincident with the onset and duration of motor neuron programmed cell death and during the period of musculature innervation and synapse formation. Hence, the data presented here identify ALK as a novel candidate receptor for regulating critical events in the development of neurons in both the central and the peripheral nervous systems.

Anaplastic Lymphoma Kinase↗
PubMed2002

Fine-needle aspiration biopsy of anaplastic large cell lymphoma, small cell variant with prominent plasmacytoid features: case report.

Anaplastic large cell lymphoma (ALCL), according to the new WHO classification, is a diagnosis limited to T/NK cell lymphomas. We present a case that demonstrates a new morphologic variant of ALCL with significant possible pitfalls for the cytopathologist. A fine-needle aspiration biopsy of a cervical lymph node showed a cellular aspiration comprised of medium-sized plasmacytoid cells in a discohesive and focally loosely cohesive pattern. The cytologic diagnosis confirmed the presence of malignancy and noted the prominent plasmacytoid features. An accompanying comment favored melanoma and included a broad differential. No cell block was available for immunohistochemical stains. Immunophenotyping of the subsequent excisional node biopsy showed an anaplastic lymphoma kinase (ALK)-positive ALCL. This case illustrates a new variant of ALCL. Although ALCL variants, such as small cell and lymphohistiocytic, are well recognized, the plasmacytoid features are an additional potential source for misdiagnosis. This case report shows that a cytopathologist should include ALK-positive ALCL in the differential diagnosis of plasmacytoid proliferations cell because of the clinical importance of the ALK-positive ALCL.

Biomarkers, Tumor↗
PubMed2000

Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells.

Cartilage-derived morphogenetic proteins 1 and 2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family which play an important role in embryonic skeletal development. Throughout adult life, bone marrow-derived precursor cells maintain their ability to differentiate into osteoblasts in response to local growth factors. This study examines the osteogenic potential of CDMP-1, CDMP-2, BMP-6 and osteogenic protein 1 (OP-1) in bone marrow stromal cells (BMSC) and investigates the endogenous expression of CDMPs/BMPs and their respective activin receptor-like kinase (ALK) receptors. A 4-day exposure of BMSC to CDMP-1, CDMP-2, BMP-6, and OP-1 under serum-free conditions stimulated the progression of the osteogenic lineage in a dose-dependent manner as evaluated by alkaline phosphatase activity and osteocalcin synthesis. In contrast to the BMPs, CDMP-1 and especially CDMP-2 were significantly less osteogenic, as confirmed by Northern blot analysis. Moreover, BMSC were shown to express endogenously CDMP-2, BMP-2 to -6 and ALK-1, -2, -3, -5 and -6. Phenotypic characterization of BMSC by RT-PCR showed transcripts of the fat marker adipsin and the prechondrocytic marker procollagen type IIA; however, we were unable to detect the mature cartilage markers, procollagen type IIB and aggrecan, even after growth factor treatment. Our data indicate that CDMP-1, CDMP-2, BMP-6 and OP-1 enhance the osteogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than BMPs. The endogenous expression of a variety of CDMPs/BMPs and their respective ALK receptors, suggests a possible involvement of these growth factors in the osteogenic differentiation of bone marrow progenitor cells.

Activin Receptors↗
PubMed1984

Physical structure, genetic content and expression of the alkBAC operon.

We cloned sequences of the alk (alkane utilization) operon of Pseudomonas and characterized them physically and genetically. These sequences were used to construct a DNA restriction map of the alkBAC region. We physically mapped alk::Tn7 insertions and delta alkBA deletions, and we were able to show complementation or marker rescue of alk point mutations by cloned DNA sequences. Our results confirmed the existence of an operon containing structural loci encoding activities for membrane alkane hydroxylase component (alkB), soluble alkane hydroxylase component (alkA) and membrane alcohol dehydrogenase (alkC). Physical mapping of alkC::Tn7 insertions and complementation of alkC point mutations by cloned sequences from the alkBA region showed that we were previously mistaken in inferring the existence of a separate unlinked alkC cluster. Studies with an alkB-lacZ transcription fusion construct established that the operon is transcribed in the order alkBAC and is under positive regulation by alkR regulatory functions.

Alkanes↗
PubMed1981

Carcinoplacental alkaline phosphatase in malignant and premalignant conditions of the human digestive tract.

The presence of carcinoplacental alkaline phosphatase (CP Alk P) was demonstrated in the cells of malignant and premalignant states of the human stomach, colon and rectum using the immunoperoxidase technique. It was shown to be present in 7 out of 18 carcinomas of stomach and 7 of 17 cases of carcinoma of colon and rectum. In the putative premalignant states it was demonstrated in 4 of 15 cases of intestinal metaplasia associated with gastric carcinoma, and 9 of 12 tubulovillous adenomas of colon. However, it was also demonstrated in 5 of 8 metaplastic polyps of colon which are not neoplastic and in 9 of 17 cases of intestinal metaplasia not associated with cancer of the stomach. It was not seen in normal gastric mucosa and only faintly in 1 of 11 samples of normal colon. CP Alk P has been shown to be a specific marker of malignancy in a wide range of human cancers when studied in sera from patients or in tissue culture of tumour cells. In this study however, although a statistical difference exists between normal and diseased tissue the marker appears as frequently in non-neoplastic states. It is concluded that CP Alk P is, in tissues, a marker of proliferative activity in cells, rather than neoplastic or malignant change. In this respect it is similar in some respects to carcinoembryonic antigen, but not other markers of placental origin such as pregnancy specific beta, glycoprotein.

Adenoma↗
PubMed1996

Hydrocarbon chain distribution of ether phospholipids of the ascidian Halocynthia roretzi and the sea urchin Strongylocentrotus intermedius.

The contents and compositions of the 1-O-alk-1'-enyl-2-acyl, 1-O-alkyl-2-acyl, and 1,2-diacyl glycerophospholipids in the muscle and viscera of the ascidian Halocynthia roretzi, and of the gonad of the sea urchin Strongylocentrotus intermedius, which are eaten to some extent in Alaska and in Asia, were analyzed by gas-liquid chromatography. 1-O-Alk-1'-enyl-2-acyl glycerophospholipids were found in all of the samples, accounting for 64.4-69.0% of the ethanolamine glycerophospholipid (EPL). By contrast, the levels of the 1-O-Alk-1'-enyl-2-acyl choline glycerophospholipids (CPL) were low (3.1-5.7%). CPL was rich in the 1-O-alkyl-2-acyl subclass amounting to 12.5-23.9% in the ascidian sample. The level of CPL in the sea urchin gonad was extremely high, amounting to 46.1%. The most prominent alkyl chains in the sn-1 position of CPL from the ascidian muscle were 16:0 (44.6%), 18:1 (26.5%), and 18:0 (10.7%), and of CPL from the sea urchin gonad were 18:0 (36.2%), 16:0 (33.0%), and 18:1 (17.8%). Unusually high levels of odd-numbered alkyl chains, e.g., 19:0 and anteiso 17:0, were detected in the CPL of all samples. The prominent alkenyl chains of EPL were 18:0 (69.4%), 16:0 (10.0%), and 18:1 (8.54%) (not counting the vinyl double bond) for the sea urchin gonad. Relatively high levels of 20:1 alkenyl chains were also present. The glycerol sn-2 positions contained high proportions of polyunsaturated fatty acids. Thus, 20:5n-3 (43.6%) and 22:6n-3 (20.1%) were most abundant in the alkylacyl CPL from the ascidian muscle and 20:5n-3 (54.9%) and 20:4n-6 (30.1%) in alkylacyl CPL from the sea urchin gonad. Despite a possible interconversion of the alkyl and alkenyl chains of each class of the ether phospholipids, they showed few features in common.

Animals↗
PubMed1977

Lipid and fatty acyl composition of rat brain capillary endothelia isolated by a new technique.

A method is described for the isolation of pure capillary endothelia from rat brain and the phosphlipid composition of these cells is reported. This method is rapid and requires only a small amount of starting material. It involves: (a) tissue disruption by high speed homogenization, (b) separation of the capillary endothelia from other brain structures using sucrose gradients, and (c) a final purification using a glass bead column. Choline and ethanolamine phosphoglycerides were found to be the predominant lipid classes of these cells amounting to 31.9% and 24.4%, respectively, of total phospholipids. The choline phosphoglycerides consisted almost exclusively of 1,2-diacyl glycerophosphorylcholine, whereas the ethanolamine phosphoglycerides consisted of approximately equal amounts of 1,2-diacyl and 1-alk-1'-enyl-2-acyl glycerophosphorylethanolamine. The composition of the constituent fatty acids of both choline and ethanolamine phosphoglycerides and the alk-1-enyl composition of ethanolamine phosphoglycerides is reported. Saturated fatty acids accounted for 45% of the total fatty acids in choline phosphoglycerides and for 53% in ethanolamine phosphoglycerides. Arachidonic acid accounted for approximately 48% of the total fatty acids in alk-1-enyl ethanolamine phosphoglyceride.

Animals↗
PubMed1982

Ether lipid content and fatty acid distribution in rabbit polymorphonuclear neutrophil phospholipids.

This study was undertaken to determine if rabbit neutrophils contain sufficient ether-linked precursor for the synthesis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) by a deacylation-reacylation pathway. The phospholipids from rabbit peritoneal polymorphonuclear neutrophils were purified and quantitated, and the choline-containing and ethanolamine-containing phosphoglycerides were analyzed for ether lipid content. Choline-containing phosphoglycerides (37%), ethanolamine-containing phosphoglycerides (30%), and sphingomyelin (28%) were the predominant phospholipid classes, with smaller amounts of phosphatidylserine (5%) and phosphatidylinositol (less than 1%). The choline-linked fraction contained high amounts of 1-O-alkyl-2-acyl-(46%) and 1,2-diacyl-sn-glycero-3-phosphocholine (54%), with a trace of the 1-O-alk-1'-enyl-2-acyl species. The ethanolamine-linked fraction contained high amounts of 1-O-alk-1'-enyl-2-acyl-(63%) and 1,2-diacyl-sn-glycero-3-phosphoethanolamine (34%), and a low quantity of the 1-O-alkyl-2-acyl species (3%). The predominant 1-O-alkyl ether chains found in the sn-1 position of the choline-linked fraction were 16:0 (35%), 18:0 (14%), 18:1 (26%), 20:0 (16%), and 22:0 (9%). The major 1-O-alk-1'-enyl ether chains found in the sn-1 position of the ethanolamine-linked fraction were 14:0 (13%), 16:0 (44%), 18:0 (27%), 18:1 (12%) and 18:2 (3%). The major acyl groups in the sn-1 position of 1,2-diacyl-sn-glycero-3-phosphocholine and 1,2-diacyl-sn-glycero-3-phosphoethanolamine were 16:0, 18:0 and 18:1. The most abundant acyl group in the sn-2 position of all classes of choline- and ethanolamine-linked phosphoglycerides was 18:2. Although this work does not define the biosynthetic pathway for platelet activating factor, it does show that there is ample precursor present to support its synthesis by a deacylation-reacylation pathway.

Animals↗
PubMed1990

Serum markers of bone formation in parenteral nutrition patients.

Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r = 0.24, p = NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r = 0.89, P less than 0.01, n = 11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r = 0.60, P = 0.05, n = 11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.

1-Carboxyglutamic Acid↗
PubMed1989

Modulation of enzymatic activities during spontaneous and induced differentiation in a human pancreatic adenocarcinoma cell line CAPAN-1.

Different enzymatic activities were studied in the human pancreatic cancer cell line CAPAN-1 in order to analyze their relation to differentiation. Alkaline phosphatase (Alk Ph), acid phosphatase, aminopeptidase, dipeptidyl peptidase IV, acid and neutral alpha-glucosidases, and acid beta-galactosidase were present. Especially alkaline phosphatase, which we have found to be of the placental type isoenzyme, is being highly expressed. Spontaneous cell differentiation at confluence as well as differentiating agents: sodium butyrate and DMSO, modulated the levels of three enzymes: Alk. Ph., aminopeptidase, and acid alpha-glucosidase. The exposure of the cells to the differentiating agents amplified the modulations occurring during the spontaneous differentiation. Aminopeptidase and acid alpha-glucosidase were found to be induced by differentiation. Alk Ph specific activity was significantly increased by the spontaneous and the butyrate-induced differentiations; whereas DMSO exerted an opposite effect, probably related to its biphasic action on cell proliferation.

Adenocarcinoma↗
PubMed2002

Mapping of a gene responsible for the difference in amylopectin structure between japonica-type and indica-type rice varieties.

The present investigation revealed that the alk and gel(t) genes, which cause the differences between a japonica rice variety Nipponbare and an indica rice variety Kasalath in terms of the disintegration of endosperm starch granules in alkali solution and their gelatinisation in a 4 M urea solution, respectively, cosegregated in backcross inbred lines derived from a cross between the two varieties. The segregation pattern of the profile for amylopectin chain-length, which was distinguished by enrichment in short chains of DP<==11 and depletion in intermediate-size chains of 12<==DP<==24 in japonica as compared with indica, was exactly the same as those of the above physico-chemical properties of starch granules, and the gene was designated as acl(t). Gene-mapping analysis showed that the starch synthase IIa ( SSIIa) gene is located at the alk locus on chromosome 6 in the rice genome. These results lead us to the possibility that different alleles of the SSIIa gene are responsible for differences in amylopectin structure between the two varieties, in that SSIIa plays a distinct role in the elongation of short chains within clusters (A+B(1) chains) of amylopectin. It is proposed that the activity of SSIIa in japonica rice is reduced in amount or functional capacity relative to the activity of this enzyme in indica rice. This, in turn, would explain why starch from japonica rice has a lower gelatinisation temperature than starch from indica rice and is more susceptible to disintegration in alkali or urea. The evidence for this hypothesis is that the alk(t), gel(t), acl(t) and SSIIa genes all map to the same locus.

Journal Article↗
PubMed1999

Anaplastic large-cell lymphoma with rapid evolution to leukemic phase.

Anaplastic large-cell lymphoma (ALCL) is a lymphoproliferative disorder that frequently presents with disseminated disease and extranodal involvement. Rare atypical cells have been detected in the peripheral blood in occasional cases. However, the presence of a prominent leukemic phase is extremely rare in these patients. We describe a patient with a small-cell variant of ALCL of T-cell phenotype, ALK-1 positive, who developed a rapid leukemic phase in association with the progression of the disease. Similar to the nodal biopsy, the predominant cells in bone marrow and peripheral blood were small atypical lymphoid cells. The large tumor cells expressed ALK immunoreactivity with a cytoplasmic and nuclear pattern, whereas some of the small cells showed only a nuclear-restricted pattern of staining. An RT-PCR study detected the NPM-ALK chimeric product in the nodal biopsy and in a peripheral blood sample in the early phase of the disease, but it became negative in a peripheral blood sample obtained after completion of the chemotherapy treatment, suggesting that this assay may be useful in the follow-up of these patients. This case indicates that a prominent leukemic phase may develop in ALCL as a manifestation of tumor dissemination and that it may be composed of a predominant small-cell atypical component.

Adult↗
PubMed2005

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that usually occurs in children and young adults. Anaplastic lymphoma kinase (ALK) abnormalities in IMT, determined using immunohistochemistry and/or molecular genetic studies, including fluorescence in situ hybridization (FISH), have almost been limited to children and young adults. In elderly cases of IMT, these ALK abnormalities are very rare. We report on a case of IMT arising in the posterior mediastinum of a 59-year-old Japanese man that showed ALK abnormalities determined using immunohistochemistry and FISH, suggesting the neoplastic nature of a subset of IMTs in older patients similar to those in younger ones and the presence of an additional mechanism(s) that allows them to start to grow late.

Anaplastic Lymphoma Kinase↗
PubMed1976

Ether lipid content of phosphoglycerides from the retina and brain of chicken and calf.

Phospholipid contents and compositions were determined for chicken and calf retinas, chicken brain and calf gray matter. Retinal phospholipid compositions differ from brain phospholipid compositions by including a higher percentage of choline phosphoglycerides and lower percentages of ethanolamine and serine phosphoglycerides. The proportion of sphingomyelin is lower in calf retina than in calf brain. Among the ethanolamine phosphoglycerides, the proportions of the alk-1-enylacyl (plasmalogen) type are lower and the proportions of alkylacyl and diacyl types are higher in retina than in brain. The alkyacyl glycerophosphoethanolamines accounted for 7.6% and 8.9% of the ethanolamine phosphoglycerides from chicken and calf retinas respectively. Lower proportions of plasmalogens in the choline phosphoglycerides were found in retina as compared with brain. The alkylacyl glycerylphosphocholines comprised 4.0% of the retinal choline phosphoglycerides. Overall, a smaller proportion of retinal phosphilipids than of brain phospholipids contained alkyl or alk-1-enyl ether groups and the ratio of alkyl groups to alk-1-enyl groups was greater in retina than in brain.

Animals↗
PubMed1980

Structure and metabolism of phospholipids in bovine epididymal spermatozoa.

Lipid analysis of bovine epididymal spermatozoa showed relatively large amounts of alkylacyl- and alk-1-enylacylglycerols in their choline and ethanol-amine phospholipids and alkylacylglycerol as the major constituent of a glycolipid tentatively identified as a monogalactosyl sulfate. The ether lipids exhibited remarkably simple molecular structures, i.e., the phospholipids had only 16:0 as alkyl and alk-1-enyl groups and their constituent fatty acids were almost exclusively 22:5 (n-6) and 22:6 (n-3). The glycolipid had mainly 16:0 as both alkyl and acyl moieties. In contrast, the diacyl choline and ethanolamine phosphoglycerides exhibited a much more complex fatty acid composition. 1,2-Diacylglycerols were the major nonpolar glycerolipid class and their acyl groups consisted almost exclusively of 14:0, 16:0 and 18:0. Labeled glycerol and dihydroxyacetone added to the incubation medium were readily incorporated into sperm lipids under both aerobic and anaerobic conditions. In each case, diacylcholine phosphoglycerides, diacylglycerols and phosphatidic acid were the major labeled lipids. Distribution of label among the molecular species of diacylglycerols and choline phosphoglycerides resembled somewhat their natural abundance. No radioactivity was found in alkylacyl or alk-1-enylacyl glycerolipids. The ether lipids may provide stable structural components of sperm membrane while the diacyl analogs undergo degradation and resynthesis.

Animals↗
PubMed1989

Solubilization, purification and characterization of lysoplasmalogen alkenylhydrolase (lysoplasmalogenase) from rat liver microsomes.

Alkenylhydrolase (EC 3.3.2.2; EC 3.3.2.5) has been purified 200-fold to a specific activity of 8.0 mumol/min per mg from rat liver microsomes with 51% of the activity recovered. Purification was accomplished by solubilization of the membrane-associated enzyme with octylglucoside and chromatographic resolution on sequential DEAE cellulose and hydroxylapatite (HPLC) columns in the presence of octylglucoside. The partially purified enzyme, specific for the 2-deacylated plasmalogen, lysoplasmalogen (1-alk-1'-enyl-sn-glycero-3-phosphocholine or -ethanolamine), had no hydrolytic activity with intact plasmalogens or 1-acyl-sn-glycero-3-phosphoethanolamine. Kinetic analyses of enzymic activity demonstrated apparent Km values of 5.5 and 42 microM for 1-alk-1'-enyl-sn-glycero-3-phosphocholine and 1-alk-1'-enyl-sn-glycero-3-phosphoethanolamine, respectively. The Vmax values were 11.7 and 13.6 mumol/min per mg with the choline and ethanolamine substrates, respectively. The optimal pH range was between 6.6 and 7.1 with both substrates; the energy of activation for the purified enzyme was 15,200 cal. The enzyme required no cofactors and was unaffected by low millimolar concentrations of Ca2+, Mg2+, Mn2+ or EDTA. It was inhibited by the sulfhydryl-reacting reagent, p-chloromercuribenzoate. Mono- or diradylglycerophospholipids or sphingomyelin did not affect the enzymic activity at 37 degrees C. Activity of the purified enzyme, destroyed by freezing at -20 degrees C, was preserved if stored at this temperature in the presence of 300-600 microM diradylglycerophosphocholine or 50% glycerol. A continuous spectrophotometric assay, adapted in our laboratory for the assay of liver alkenylhydrolase, facilitated this purification. This is the first reported purification of alkenylhydrolase.

Animals↗
PubMed1991

Arachidonic acid metabolism during antigen and ionophore activation of the mouse bone marrow derived mast cell.

This study has examined the metabolism of arachidonic acid in the mouse bone marrow-derived mast cell (BMMC) during immunologic and nonimmunologic activation. The predominant pools of endogenous arachidonate in the mast cells were found in ethanolamine (46%), choline (39%) and inositol (14%) containing glycerolipids. Initial studies established conditions where equilibrium labelling of these major phospholipids in the BMMC could be reached. Upon challenge, arachidonate was lost from all major phospholipid classes (phosphatidylethanolamine greater than phosphatidylcholine greater than phosphatidylinositol). There was a small but significant increase in the amount of label associated with phosphatidic acid during cell activation. Arachidonate was distributed among 1-acyl, 1-alkyl and 1-alk-1-enyl-linked subclasses of PC and PE. The rank order of loss of labelled arachidonate from the major PE and PC subclasses during antigen and ionophore activation was 1-alk-enyl-2-arachidonoyl-GPE greater than 1-acyl-2-arachidonoyl-GPC greater than 1-acyl-2-arachidonoyl-GPE greater than 1-alkyl-2-arachidonoyl-GPC. Labelled products released into the supernatant fluids and free arachidonic acid within the cell accounted for the bulk of arachidonate lost from phospholipids. Labelled products in the supernatant fluids were composed of LTB4, LTC4, PGD2 and free arachidonic acid. BMMC phospholipids were also labelled for 24 hr with [3H]choline, [3H]myoinositol or [14H]ethanolamine and labelled 2-lyso phospholipids were measured after cell activation. Radioactivity in lysophospholipids from PC, PE and PI increased significantly between 30 s and 2 min after antigen activation and then declined. Taken together, these studies suggest that arachidonate is mobilized predominantly from PE and in particular 1-alk-1-enyl-2-arachidonoyl-GPE by the direct removal of arachidonate from the sn-2 position of the molecule. Most of this arachidonate is then released from cells as eicosanoids or free fatty acid.

Animals↗
PubMed1992

Synthesis of platelet activating factor and metabolism of related lipids in embryonic cells.

Primary cultures of mouse embryo palate mesenchyme (MEPM) cells incubated with 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine ([3H])lyso-PAF) incorporated radiolabel into 1-radyl-2-acyl-sn-glycero-3-phosphocholine (PC) and -phosphoethanolamine (PE). The radiolabeled PC was insensitive to hydrolysis with HCl fumes, whereas at least 82% of the 3H found in the PE was hydrolyzed to 3H-aldehydes by such treatment. Treatment of the PC with Vitride produced [3H]alkylglycerol; similar treatment of the PE produced [3H]alk-1-enylglycerol. None of the radiolabeled products yielded fatty alcohol upon reduction with Vitride. These findings indicate the radiolabeled PC was 1-O-alkyl-linked whereas the PE contained predominantly 1-O-alk-1'-enyl species with smaller amounts of 1-O-alkyl species. Homogenates of MEPM cells which had been prelabeled with [3H]lyso-PAF and [14C]arachidonic acid produced 14C-fatty acid, [3H]lyso-PC, and [3H]alkylglycerol when incubated at selected values of pH and concentrations of calcium. There was no accumulation of [3H]lyso-PE in the various incubation mixtures. Stimulation of MEPM cells with the ionophore A23187 in the presence of calcium and [3H]acetate resulted in the production of 3H-platelet-activating factor (PAF), identified by its migration with authentic PAF and its conversion to 1-O-[3H]alkyl-2,3-diacetylglycerol upon treatment with phospholipase C and acetic anhydride. These studies demonstrate that: (i) MEPM cells are able to incorporate [3H]lyso-PAF into 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine, the storage form of PAF, and into 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (PE plasmalogen); (ii) endogenous 1-O-[3H]alkyl-2-acyl-sn-glycero-3-phosphocholine can serve as a substrate for phospholipase A2 in homogenates; and (iii) MEPM cells have the ability to synthesize PAF, thus raising the possibility that this compound may play a role in modulating the physiology of these embryonic cells.

Animals↗