Serum glypican4 and glycosylphosphatidylinositol-specific phospholipase D levels are associated with adipose tissue insulin resistance in obese subjects with different glucose metabolism status.

OBJECTIVES: Glypican4 (GPC4) is a novel adipokine associated with obesity and insulin resistance. GPC4 was cleaved by the glycosylphosphatidylinositol-specific phospholipase D (GPLD1) in an anchored site of the glycosylphosphatidylinositol, and then was released into the extracellular environment. Herein, we investigated the changes of serum GPC4 and GPLD1 levels in obese subjects with different glucose metabolism status and their relationship with adipose tissue insulin resistance index (Adipo-IR) in Chinese north populations. METHODS: A total of 221 obese subjects and 37 normal controls (NC) were recruited in this study. Obese subjects were divided into normal insulin (NI) group, hyperinsulinemia (HI) group, impaired glucose tolerance (IGT) group, and type 2 diabetes mellitus (DM) group. Serum GPC4, GPLD1, and adiponectin were determined by commercially available ELISA kits. RESULTS: Serum GPC4 levels in the HI, IGT, and DM groups were significantly higher than those in the NC and NI groups (2.27 ± 0.58 ng/mL, 2.21 ± 0.60 ng/mL, 2.49 ± 0.67 ng/mL vs. 1.70 ± 0.33 ng/mL, 1.93 ± 0.34 ng/mL, P < 0.05). GPC4 was positively correlated with GPLD1, which was the most important influencing factor of GPC4. Adipo-IR was independently and positively associated with serum GPC4 and GPLD1. For GPC4, after adjustment for confounders, the risk of adipose tissue insulin resistance in subjects with the highest tertile was 2.974-fold that of those with the lowest tertile (OR = 2.974, P = 0.013). For GPLD1, before adjustment for lipids, the increased probability still existed (Model 2, OR = 3.568, P = 0.003). CONCLUSION: GPC4 is an adipokine associated with adipose tissue insulin resistance, and its activity may be regulated by GPLD1. GPC4 may be a marker for adipose tissue insulin resistance in Chinese north obese populations.

Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain.

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.

Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum.

Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3 ± 1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPARα-immunoreactive neurons in the striatum. Ethanol-related neurobiological alterations such as a reduction in the number of microglial cells expressing iNOS (a cytokine-inducible immune defense) and in adult neural stem/progenitor cell (NSPC) proliferation (phospho-H3 and BrdU) and maturation (BrdU/ß3-tubulin), as well as an increase in damage cell activity (FosB) and apoptosis (cleaved caspase 3) were also observed in the rat striatum. Pharmacological administration of OEA (10 mg/kg) for 5 days during ethanol exposure exacerbated ethanol-induced hypolocomotion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPARα-positive cell population and NSPC proliferation and maturation. OEA also decreased astrocyte-related vimentin immunoreactivity and increased microglial cell population (Iba-1, iNOS) in the striatum. These results suggest that OEA-PPARα signaling modulates glial activation, cell apoptosis and NSPC proliferation and maturation in response to striatal-specific neurobiological alterations induced by prolonged ethanol intake in rats.

Phospholipase D1 expression analysis in relapsing-remitting multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including ß-interferons (IFNß) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid. It has an established function in regulation of immune response. In the present study we have evaluated PLD1 transcript levels and plasma concentrations in 78 relapsing-remitting MS (RRMS) patients as well as 78 normal age- and sex-matched healthy subjects using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Significant PLD1 down-regulation has been observed in total MS patients compared with controls (P < 0.001) as well as IFN-ß responders (P = 0.034) and non-responders (P < 0.001) compared with controls, respectively. However, a significant up-regulation has been detected in IFN-ß responders compared with non-responders (P = 0.047). In both males and females groups, significant down-regulations have been detected in patients compared with controls (P = 0.014 and P = 0.002, respectively). The same results have been detected in PLD1 plasma concentrations. In conclusion, PLD1 transcripts in blood and its plasma concentrations can be used as putative biomarkers for evaluation of therapeutic responses to IFN-ß in RRMS patients. However, this result should be validated in future studies.

The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA); however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM). In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM) to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset 'classic' T1DM (n = 156), LADA (n = 174), T2DM (n = 195) and healthy cohorts (n = 166). Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ) together with liquid chromatography tandem mass spectrometry (LC-MS) to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0%) proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1), which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM.

Regulation of glycosylphosphatidylinositol-anchored proteins and GPI-phospholipase D in a c-Myc transgenic mouse model of hepatocellular carcinoma and human HCC.

Recent research implicated glycosylphosphatidylinositol-anchored proteins (GPI-AP) and GPI-specific phospholipase D (GPI-PLD) in the pathogenesis of fatty liver disease and hepatocellular carcinoma (HCC). Given that c-Myc is frequently amplified in HCC, we investigated their regulation in a c-Myc transgenic disease model of liver cancer and HCC patient samples. Whole genome scans defined 54 significantly regulated genes coding for GPI-AP of which 29 and 14 were repressed in expression in transgenic tumors and steatotic human hepatocyte cultures, respectively, to influence lipid-mediated signal transduction, extracellular matrix and immunity pathways. Analysis of gene specific promoter revealed >95% to carry c-Myc binding sites thus establishing a link between c-Myc activity and transcriptional response. Alike, serum GPI-PLD activity was increased 4-fold in transgenic mice; however its tissue activity was reduced by 70%. The associated repression of the serine/threonine phosphatase 2A (PP2A), i.e. a key player of c-Myc proteolysis, indicates co-ordinate responses aimed at impairing tissue GPI-PLD anti-proliferative activities. Translational research identified >4-fold increased GPI-PLD serum protein expression though enzyme activities were repressed by 60% in NASH and HCC patients. Taken collectively, c-Myc influences GPI-AP signaling transcriptionally and posttranslational and represses GPI-AP anti-proliferative signaling in tumors. The findings broaden the perspective of molecular targeted therapies and disease monitoring.

Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

BACKGROUND: Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy. METHODS: The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases. RESULTS: The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P <0.001), and serum levels of TNF-α (P <0.001) and interleukin-6 (P <0.001) after ADA medication, although plaque levels were comparable. Among a total of 495 protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P <0.01). CONCLUSION: These results suggest a beneficial effect of ADA therapy on the periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

Discovery of a novel circulating biomarker in patients with abdominal aortic aneurysm: a pilot study using a proteomic approach.

Abdominal aortic aneurysm (AAA) is a common condition with high mortality when ruptured. Most clinicians agree that small AAAs are best managed by ultrasonographic surveillance. However, it has been stated in recent reviews that a serum/plasma biomarker that predicts AAA rupture risk would be a powerful tool in stratifying patients with small AAA. Identification of such circulating biomarkers has been to date unsuccessful. In this study, we used a proteomic approach to find new, potential plasma AAA biomarker candidates. Prefractionated plasma samples were analyzed by two-dimensional differential in-gel electrophoresis to identify differentially expressed proteins between four patients with small AAA and four controls without aneurysm. Protein spots that differed significantly between patients and controls were selected and identified by mass spectrometry. Three protein spots had significantly different expression between patients and controls. The most interesting finding was that patients with small AAA had increased levels of the enzyme glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) compared with the controls without aneurysm. In conclusion, by using a proteomic approach, this pilot-study provides evidence of GPI-PLD as a novel potential plasma biomarker for AAA.

Genetic variation of GPLD1 associates with serum GPI-PLD levels: a preliminary study.

HDL is a heterogeneous mixture of lipoprotein particles varying in composition, size, and function. We and others have described a small (7.0nm), minor (0.1% of total apolipoprotein AI) particle containing apolipoprotein AI, AIV and glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in humans the function of which is not entirely known. Circulating GPI-PLD levels are regulated by multiple factors including genetics. To determine if genetic variation in GPLD1 affects circulating GPI-PLD levels, we examined the relationship between 32 SNPS upstream, within, and downstream of GPLD1 and circulating GPI-PLD levels in Caucasians (n=77) and African-Americans (n=99). The genotype distribution among races differed at 13 SNPs. Nine SNPS were associated with circulating GPI-PLD levels in Caucasians but not African-Americans. These results suggest that genetic variation of GPLD1 appears to associate with circulating GPI-PLD levels. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).

Procoagulant and prothrombotic activation of human erythrocytes by phosphatidic acid.

Increased phosphatidic acid (PA) and phospholipase D (PLD) activity are frequently observed in various disease states including cancers, diabetes, sepsis, and thrombosis. Previously, PA has been regarded as just a precursor for lysophosphatidic acid (LPA) and diacylglycerol (DAG). However, increasing evidence has suggested independent biological activities of PA itself. In the present study, we demonstrated that PA can enhance thrombogenic activities in human erythrocytes through phosphatidylserine (PS) exposure in a Ca(2+)-dependent manner. In freshly isolated human erythrocytes, treatment of PA or PLD induced PS exposure. PA-induced PS exposure was not attenuated by inhibitors of phospholipase A(2) or phosphatidate phosphatase, which converts PA to LPA or DAG. An intracellular Ca(2+) increase and the resultant activation of Ca(2+)-dependent PKC-alpha appeared to underlie the PA-induced PS exposure through the activation of scramblase. A marginal decrease in flippase activity was also noted, contributing further to the maintenance of exposed PS on the outer membrane. PA-treated erythrocytes showed strong thrombogenic activities, as demonstrated by increased thrombin generation, endothelial cell adhesion, and erythrocyte aggregation. Importantly, these procoagulant activations by PA were confirmed in a rat in vivo venous thrombosis model, where PA significantly enhanced thrombus formation. In conclusion, these results suggest that PA can induce thrombogenic activities in erythrocytes through PS exposure, which can increase thrombus formation and ultimately contribute to the development of cardiovascular diseases.

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women.

Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor high-density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating GPI-PLD levels. The objective of the study was to determine the effect of weight loss and changes in insulin sensitivity on plasma GPI-PLD levels. Forty-two nondiabetic obese women were included in the study, which involved a 3-month dietary intervention randomizing patients to a low-fat or a low-carbohydrate diet. The study's main outcome measures were plasma GPI-PLD levels and insulin sensitivity as estimated by the homeostasis model assessment. The very low carbohydrate diet group lost more weight after 3 months (-7.6 +/- 3.2 vs -4.2 +/- 3.5 kg, P < .01), although the decrease in insulin resistance was similar between groups. Weight loss with either diet did not alter plasma GPI-PLD levels. However, baseline GPI-PLD levels correlated with the change in insulin sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity correlated with the change in insulin sensitivity in response to the low-carbohydrate diet. Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity.

The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes.

Diacylglycerides (DAGs) such as 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulate 5-lipoxygenase (5-LO) enzyme activity and function as agonists for human polymorphonuclear leukocytes (PMNL) to induce 5-LO product synthesis. Here, we addressed the role of endogenous DAG generation in agonist-induced 5-LO activation in human PMNL. Preincubation of PMNL with the phospholipase D (PLD) inhibitor 1-butanol potently suppressed 5-LO product synthesis induced by the Ca(2)(+) ionophore A23187 or thapsigargin (TG) and blocked A23187-evoked translocation of 5-LO from the cytosol to the nuclear membrane, analyzed by subcellular fractionation as well as by indirect immunofluorescence microscopy. Tertiary-butanol, a rather poor inhibitor of PLD, caused only moderate suppression of 5-LO and hardly inhibited 5-LO translocation. Interestingly, 1-butanol failed to inhibit 5-LO product formation when PMNL were stimulated with OAG (30 microM). Moreover, coincubation of A23187- or TG-stimulated PMNL with OAG reversed inhibition of 5-LO product formation by 1-butanol in a concentration-dependent manner (EC(50), approximately 1 muM) and also restored 5-LO translocation. In addition, inhibition of phosphatidic acid phosphatase (PA-P) by propranolol or bromoenol lactone caused suppression of 5-LO product formation and of translocation, which could be reversed by addition of exogenous OAG. Together, our data suggest that in agonist-stimulated PMNL, the endogenous formation of DAGs via the PLD/PA-P pathway determines 5-LO activation.

Statin therapy reduces serum levels of glycosylphosphatidylinositol-specific phospholipase D.

Statin therapy is associated with changes in low-density, very low-density, and high- density lipoprotein metabolism. The effect of statin therapy on a minor high-density lipoprotein particle containing glycosylphosphatidylinositol-specific phospholipase D has not been examined. Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) has been implicated in triglyceride metabolism. A double-blind, crossover design comparing the effect of simvastatin (80 mg) and atorvastatin (80 mg) on serum lipid and glycosylphosphatidylinositol-specific phospholipase D levels was conducted in 13 patients with low high-density lipoproteins. Both statins reduced cholesterol, triglycerides, and apolipoprotein B and significantly lowered serum glycosylphosphatidylinositol-specific phospholipase D levels (16%). This statin effect seems to occur in the plasma compartment as neither statin altered GPI-PLD mRNA levels in HepG2 cells. Serum glycosylphosphatidylinositol-specific phospholipase D levels are regulated by statins and may represent an additional biochemical mechanism for affecting serum triglyceride levels.

Glycosylphosphatidylinositol-specific phospholipase d in nonalcoholic Fatty liver disease: a preliminary study.

CONTEXT: Recent studies demonstrated that de novo lipogenesis is increased in patients with nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD also have plasma lipid abnormalities. These lipid abnormalities may in part be related to insulin resistance, which is common in patients with NAFLD. Insulin resistance is associated with alterations in proteins involved in lipid metabolism including glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), which is involved in triglyceride metabolism. OBJECTIVE: The objective of the study was to determine whether alterations in serum and hepatic levels of GPI-PLD occur in patients with NAFLD. DESIGN AND PATIENTS: We examined the following: 1) levels of serum GPI-PLD in nondiabetics with nonalcoholic steatohepatitis, compared with matched controls; 2) hepatic expression of GPI-PLD mRNA in patients with normal liver or NAFLD; and 3) effect of overexpressing GPI-PLD vs. beta-galactosidase (control) on global gene expression in a human hepatoma cell line. RESULTS: The serum levels of GPI-PLD were significantly higher in patients with nonalcoholic steatohepatitis than in matched controls (119 +/- 24 vs.105 +/- 15 microg/ml, P = 0.047). The hepatic expression of GPI-PLD mRNA was increased nearly 3-fold in NAFLD patients, compared with patients with normal liver (3.1 +/- 2.6 vs. 1.1 +/- 1.0 arbitrary units per microgram total RNA, P = 0.026). Finally, overexpressing GPI-PLD was associated with an increase in de novo lipogenesis genes. CONCLUSIONS: Patients with NAFLD have elevated serum levels and hepatic expression of GPI-PLD, and its overexpression in vitro is associated with increased expression of de novo lipogenesis genes. These results suggest that GPI-PLD may play a role in the pathogenesis of NAFLD and/or its metabolic features and warrants further investigation.

Glycosylphosphatidylinositol-specific phospholipase D influences triglyceride-rich lipoprotein metabolism.

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a minor HDL-associated protein. Because many minor HDL-associated proteins exchange between different lipoprotein classes during the postprandial state and are also involved in triglyceride (TG) metabolism, we hypothesized that GPI-PLD may play a role in the metabolism of TG-rich lipoproteins. To test this hypothesis, we examined the distribution of GPI-PLD among lipoprotein classes during a fat tolerance test in C57BL/6 and LDL receptor-deficient (LDLR(-/-)) mice fed either a chow or high-fructose diet. In the fasting state in wild-type mice fed a chow diet, GPI-PLD was only present in HDL, whereas in LDLR(-/-) mice GPI-PLD was present in HDL and intermediate-density lipoproteins (IDL)/LDL. During the fat tolerance test, there was no change in total serum GPI-PLD levels in either model; however, a significant amount of GPI-PLD appeared in both VLDL (0.5-1% of total GPI-PLD) and IDL/LDL (5-10% of total GPI-PLD) in both models. The high-fructose diet increased both fasting and postprandial TG and serum GPI-PLD levels in both strains as well as the amount of GPI-PLD in VLDL. To determine whether GPI-PLD plays a direct role in TG metabolism, we increased liver GPI-PLD expression in C57BL/6 mice by adenovirus-mediated gene transfer, which resulted in a sevenfold increase in serum GPI-PLD levels. This change was associated with an increase in fasting (30%) and postprandial TG (50%) and a twofold reduction in TG-rich lipoprotein catabolism compared with saline or control adenovirus-treated mice. These studies demonstrate that GPI-PLD affects serum TG levels by altering catabolism of TG-rich lipoproteins.

[The plasma levels of orexigenic peptides and human platelets phospholipase D activity in anorexia nervosa patients]. / Stezenie wybranych peptydów oreksygenicznych w osoczu a aktywnosc fosfolipazy d w plytkach krwi u chorych z jadlowstretem psychicznym.

UNLABELLED: Ghrelin, orexins A and B (OXA, OXB) are neuropeptides engaged in the regulation of energy balance stimulating appetite and feeding. Disturbances in their activity are proposed to be involved in pathomechanism of eating disorders, particularly in anorexia nervosa (AN). The intracellular mechanism of the peptides action remains unclear. It is considered whether the orexigenic peptides may act through second messengers related to phospholipase D (PLD). The aim of the study was to find a hypothetical relation between ghrelin, OXA and OXB levels and human platelets PLD activity. MATERIAL AND METHODS: 25 AN females and 20 healthy controls (mean age 17.6 and 18.6, mean BMI 15.03 and 21.41 kg/m(2), respectively) were examined. OXA and OXB plasma levels and total ghrelin plasma level was determinated with RIA. PLD activity in homogenized blood platelets was assessed with modified fluorometric method. All values are presented as the mean values. The data were analyzed using Student-t test, non-parametric U-Mann-Whitney test and Spearman correlation. The p < 0.05 was accepted as the level of significance. RESULTS: There is a correlation between analyzed neuropeptides and PLD in AN patients. CONCLUSION: In AN patients it is not possible to exclude influence orexins and ghrelin on platelet PLD activity.

[Effect of GPI-PLD on adhesion function of bone marrow mononuclear cell from patients with myeloid leukemia and its mechanism].

To explore the effect of glycosyl-phosphatidyl inositol-specific phospholipase D (GPI-PLD) on the adhesion function of bone marrow mononuclear cell from patients with myeloid leukemia and analyze its mechanism, the activity of GPI-PLD in bone marrow mononuclear cell from the patients were measured by using GPI-anchored placental alkaline phosphatase (PLAP) as substrate and Triton-X114 partitioning; the adhesion rate and CD24 expression of these cells were measured by MTT and immunohistochemical method respectively, when these cells were or were not treated by 1 mmol/L 1,10-phenanthroline for 5 hours. The results showed that the GPI-PLD activity of bone marrow mononuclear cells from the patients was significantly inhibited after being treated by 1 mmol/L 1, 10-phenanthroline for 5 hours [(42.08 +/- 7.21)% vs (5.4 +/- 2.96)%], while the adhesion rate and the expression of CD24 of these cells were increased [(49.78 +/- 26.73)% vs (61.19 +/- 29.14)%, (16.02 +/- 9.68)% vs (18.5 +/- 11.14)%, respectively)]. It is concluded that depression of GPI-PLD activity can increase the adhesion rate of bone marrow mononuclear cells from the patients while the CD24 expression is enhanced.

Lysophosphatidic acid increases phosphatidic acid formation, phospholipase D activity and degranulation by human neutrophils.

I-oleoyl-sn-glycero-3-phosphate, a lysophosphatidic acid (LPA), in serum is a biologically active lipid and has multiple functions depending on the cell types. Several studies have shown that LPA stimulates phospholipase D (PLD) activity in fibroblasts and prostate cancer cells in culture. PLD plays a central role in regulating neutrophil functions. One of the functions of the lipid product, phosphatidic acid (PA), of PLD action in neutrophils is to promote degranulation. In the present study, we examined the effect of LPA on PLD activity and degranulation by human neutrophils. The results show that exogenous LPA increased PA formation, PLD activity and degranulation by human neutrophils in a time and concentration dependent manner. These findings suggest that LPA released from activated platelets during blood clotting may participate in bacterial killing and wound healing process. On the other hand, augmented LPA production might be involved in inflammation, causing damage of the host tissues.