Platelet-activating Factor Acetylhydrolase Activity Research Articles

Cloning and Expression of cDNA Encoding Rat Liver 60-kDa Lysophospholipase Containing an Asparaginase-like Region and Ankyrin Repeat

Mammalian tissues contain small form and large form lysophospholipases. Here we report the cloning, sequence, and expression of cDNA encoding the latter form of lysophospholipase using antibody raised against the enzyme purified from rat liver supernatant (Sugimoto, H., and Yamashita, S. (1994) J. Biol. Chem. 269, 6252-6258). The 2,539-base pair cDNA encoded 564 amino acid residues with a calculated Mr of 60,794. The amino-terminal two-thirds of the deduced amino acid sequence significantly resembled Escherichia coli asparaginase I with the putative asparaginase catalytic triad Thr-Asp-Lys and was followed by leucine zipper motif. The carboxyl-terminal region carried ankyrin repeat. When the cDNA was transfected into HEK293 cells, not only lysophospholipase activity but also asparaginase and platelet-activating factor acetylhydrolase activities were expressed. Reverse transcription-polymerase chain reaction revealed that the transcript occurred at high levels in liver and kidney but was hardly detectable in lung and heart from which large form lysophospholipases had been purified, suggesting the presence of multiple forms of large form lysophospholipase in mammalian tissues.

Identification of a major PAF acetylhydrolase in human serum/plasma as a 43 kDa glycoprotein containing about 9 kDa asparagine-conjugated sugar chain(s).

Platelet-activating factor (PAF) acetylhydrolase from human serum/plasma was identified on a polyvinylidene difluoride (PVDF) membrane by electroblotting proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme activity was detected in the 43 kDa region on the membrane as a decrease in the beta-radioluminescence of [3H]acetyl-PAF or by the convenient method for determining PAF acetylhydrolase activity (the TCA precipitation method). The enzyme activity on treatment with N-glycosidase F shifted to the 34 kDa region on the PVDF membrane. On the other hand, only one band was observed, corresponding to a molecular mass of 53 kDa, on analysis by SDS-PAGE with silver staining. Treatment of the 53 kDa protein with N-glycosidase F changed its molecular mass to 43 kDa (protein A). The NH2-terminal 32 amino acid sequence of protein A completely corresponds to that of the heterogenous enzyme with 54 amino acids deleted from the NH2 terminus reported by Tjoelker et al. (Nature 374, 549-553, 1995). Even after trypsin treatment of the N-glycosidase F-digested enzyme, its PAF-AH activity remained in the 34 kDa region, but the contaminating protein A disappeared, on the PVDF membrane. In addition, the majority of serum PAF-AH was retained on a Sambucus sieboldiana agglutinin (SSA)-agarose column and was eluted with the hapten sugar, lactose. These results indicate that PAF acetylhydrolase consisting of a 34 kDa protein and about 9 kDa asparagine-conjugated sugar chain(s) is a major enzyme in human serum/plasma.

Reduced PAF-Acetylhydrolase Activity Is Associated with Postinjury Multiple Organ Failure

Reduced PAF-Acetylhydrolase Activity Is Associated with Postinjury Multiple Organ Failure

Reduced PAF-Acetylhydrolase Activity Is Associated with Postinjury Multiple Organ Failure

Reduced PAF-Acetylhydrolase Activity Is Associated with Postinjury Multiple Organ Failure

The Presence of Platelet-Activating Factor-Acetylhydrolase in Human Middle Ear Effusions

Factors related to inflammation, including platelet-activating factor (PAF), apparently have a role in chronic otitis media with effusion. PAF is metabolized to the biologically inactive lyso-PAF by the enzyme PAF-acetylhydrolase (PAF-AH). We have obtained evidence that PAF-AH activity is present in human middle ear effusions in patients with chronic otitis media with effusion. The present study revealed the enzyme in human middle ear effusions to be the plasma type PAF-AH. We suggest that PAF-AH may be involved in regulating inflammation in the middle ear by inactivating PAF, the potent proinflammatory autacoid.

Reduced Platelet-Activating Factor-Acetylhydrolase Activity in Maternal Plasma Obtained from Normotensive Pregnant Women Destined to Develop Pregnancy-Induced Hypertension

Objective: To elucidate whether plasma platelet-activating factor-acetylhydrolase (PAF-AH) activities in pregnant women who are destined to develop pregnancy-induced hypertension (PIH) are different from those in normotensive pregnant women.Study Design: We evaluated plasma PAF-AH activity in 18 nonpregnant normotensive women. We also evaluated longitudinally plasma PAF-AH activity, platelet counts, and mean platelet volume (MPV) in normotensive pregnant women at 8 weeks', 20 weeks', and 30 weeks' gestation. Plasma samples were obtained from 15 patients who ultimately developed PIH after 35 weeks' gestation (PIH subgroup), and 11 patients who remained normotensive during pregnancy (non-PIH subgroup).Results: PAF-AH activity in nonpregnant women was significantly higher (p < 0.05) than that in the non-PIH pregnant subgroup at 8 and 20 weeks' gestation. PAF-AH activity at 8,20, and 30 weeks' gestation in the PIH subgroup was significantly lower (p < 0.03) than that in the non-PIH group at each gestational week. PAF-AH activity in the PIH subgroup was positively correlated with platelet counts (p < 0.001) and negatively correlated with MPV (p < 0.02).Conclusions: Plasma PAF-AH activity is low by the first trimester in normotensive pregnant women who are destined to develop PIH, and this decreased enzyme activity may be related to platelet activation and consumption.

Possible mechanisms for the differential effects of high linoleate safflower oil and high α-linolenate perilla oil diets on platelet-activating factor production by rat polymorphonuclear leukocytes

As compared with high dietary linoleate safflower oil, high dietary α-linolenate perilla oil decreased platelet-activating factor (PAF) production by nearly half in calcium ionophore (CaI)-stimulated rat polymorphonuclear leukocytes (PMN). In the CaI-stimulated PMN from the perilla oil group, the accumulated amount of arachidonate (AA) plus eicosapentaenoate (EPA) was 30% less and that of lyso-PAF was 50% less, indicating that the decreased availability of lyso-PAF is a factor contributing to the relatively low PAF production. Consistently, eicosatetraynoic acid (ETYA), a dual inhibitor of cyclooxygenase and lipoxygenase, increased free fatty acids (FFA) and decreased PAF production possibly by decreasing the availability of lyso-PAF. Although, leukotrienes (LTs) have been proposed to stimulate PAF production synergistically, a potent LTB 4 receptor antagonist, ONO-4057, decreased the formation of free fatty acids and LTB 4, but stimulated PAF production somewhat, indicating that LTB 4 may not stimulate PAF production in PMN. Lysophospholipid-induced transacylase (CoA-independent transacylase) activity in PMN homogenates was 25∼30% lower in the perilla oil group but no significant differences were observed in the lyso-PAF acetyltransferase and PAF acetylhydrolase activities between the two dietary groups. Thus, decreased transacylase activity is another factor associated with the relatively low PAF production in the perilla oil group.

Cytokine and lipid mediator blood concentrations after coronary artery surgery.

This study investigates whether increased levels of cytokines and lipid mediators may be associated with complications after coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). Hemodynamic measurements and blood samples were obtained in 32 patients before and after the end of ECC and at the 6th and the 24th postoperative hours. Coagulation and pulmonary and cardiovascular functions were specifically assessed postoperatively at the same time. Patients with cardiovascular dysfunction had higher interleukin 8 (IL-8) levels. Higher platelet-activating factor (PAF) and decreased PAF acetylhydrolase activity (AHA, the enzyme that inactivates PAF) levels were found in patients with moderate cardiovascular dysfunction. Interleukin 6 (IL-6), IL-8, and AHA levels correlated with most hemodynamic parameters and creatine phosphokinase myocardial band levels obtained after surgery. Patients with severe lung injury had lower PAF, 6-keto prostaglandin (Pg)F1alpha, and PgE2 levels and higher thromboxane (Tx) B2 concentrations compared with patients without lung injury. Increased IL6 levels were only associated with moderate lung injury. Impaired hemostasis was associated with higher IL6 levels. AHA, IL-6, and IL-8 seem to be associated with cardiovascular dysfunction. The IL-6 blood levels and the ratio of TxB2/6 keto-PgF1alpha blood levels are increased during post-CABG lung injury. These results identify an association between specific post-CABG complications and the systemic inflammatory response. The clinical significance of this association remains to be evaluated. Patients with pulmonary, cardiovascular, or hemostasis dysfunction after cardiopulmonary bypass demonstrate aberrancies in a variety of cytokines and lipid mediators in arterial blood or plasma. The relationship between these findings and inflammatory response-induced complications remains to be determined.

Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line

The human immature K562 erythroid cell line was studied for its capacity to produce and to metabolize the phospholipid molecule platelet-activating factor (PAF). K562 cells produced PAF under calcium ionophore stimulation. Lyso PAF and acetyl-CoA (the acetate donor molecule for the acetylation of lyso PAF into PAF) had no effect on the amounts of PAF produced by ionophore-stimulated cells. The metabolism of PAF and lyso PAF by K562 cells was compared to that of freshly-isolated human bone marrow erythroblasts and blood erythrocytes. K562 cells rapidly metabolized [ 3 H ]PAF and [ 3 H ]lyso PAF with 1-alkyl analogue of phosphatidylcholine as the major metabolic product. In contrast, blood erythrocytes did not. PAF acetylhydrolase activity levels in K562 cells and bone marrow erythroblasts were similar and higher than in blood erythrocytes. PAF (1–100 nM) stimulated [ 3 H ]thymidine incorporation in K562 cells grown in low serum concentration, a non-metabolizable PAF agonist being more potent than PAF to stimulate thymidine incorporation. PAF receptor mRNA was detected in K562 cells by polymerase chain reaction on reverse transcripts. The present study demonstrates that K562 cells produce and metabolize PAF and underlines the putative role of erythroid precursors in the modulation of bone marrow PAF concentrations. The effect of PAF on the growth of K562 cells might be mediated through PAF receptors suggesting a potential role of PAF on the proliferation and functions of human erythroid marrow precursors.

PAF analogues capable of inhibiting PAF acetylhydrolase activity suppress migration of isolated rat cerebellar granule cells

Intracellular platelet-activating factor (PAF) acetylhydrolase in the bovine brain is a heterotrimeric enzyme composed of α1, α2 and β subunits. The trimeric enzyme may be involved in neural cell migration, since the human homolog of the non-catalytic β subunit is a product of the LIS-1 gene which is a causative gene for Miller–Dieker syndrome. Miller–Dieker syndrome is a form of lissencephaly that is characterized by widespread agyria of the brain and defects of neuronal cell migration. In the present study, we attempted to determine whether the catalytic activity of either the α1 or α2 subunit is required for the regulation of granule cell migration. Granule cells prepared from rat cerebellum at postnatal day 0 express all three subunit proteins ( α1, α2 and β) as determined by western blotting. Granule cell migration, which was observed in vitro on a layer coated with laminin, was effectively blocked by PAF analogs which showed PAF receptor-antagonistic activity (CV-6209 and CV-3988) and PAF receptor-agonistic activity (carbamoyl PAF). These PAF analogs also inhibited the activity of bovine brain PAF acetylhydrolase. Cell migration was restored when the inhibitors were removed by washing the treated cells with buffer, indicating that the inhibitory effect of PAF analogs is reversible. Structurally-unrelated PAF antagonists (SM-12502, TCV-309 and YM-264), none of which showed any appreciable inhibitory activity against PAF acetylhydrolase, did not block granule cell migration under the same conditions. It is suggested that the catalytic activity of PAF acetylhydrolase may play a crucial role in neural cell migration.

Cell-specific Regulation of Expression of Plasma-type Platelet-activating Factor Acetylhydrolase in the Liver

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that causes hypotension, increases vascular permeability, and has been implicated in anaphylaxis, septic shock and several other inflammatory responses. PAF is hydrolyzed and inactivated by the enzyme PAF-acetylhydrolase. In the intact rat, a mesenteric vein infusion of lipopolysaccharide (LPS) served as an acute, liver-focused model of endotoxemia. Plasma PAF-acetylhydrolase activity increased 2-fold by 24 h following LPS administration. Ribonuclease protection experiments demonstrated very low levels of plasma-type PAF-acetylhydrolase mRNA transcripts in the livers of saline-infused rats; however, 24 h following LPS exposure, a 20-fold induction of PAF-acetylhydrolase mRNA was detected. In cells isolated from endotoxin-exposed rat livers, Northern blot analyses demonstrated that Kupffer cells but not hepatocytes or endothelial cells were responsible for the increased PAF-acetylhydrolase mRNA levels. In Kupffer cells, plasma-type PAF-acetylhydrolase mRNA was induced by 12 h, peaked at 24 h, and remained substantially elevated at 48 h. Induction of neutropenia prior to LPS administration had no effect on the increase in PAF-acetylhydrolase mRNA seen at 24 h. Although freshly isolated Kupffer cells contain barely detectable levels of plasma-type PAF-acetylhydrolase mRNA, when Kupffer cells were established in culture, PAF-acetylhydrolase expression became constitutively activated concomitant with cell adherence to the culture plates. Alterations in plasma-type PAF-acetylhydrolase expression may constitute an important mechanism for elevating plasma PAF-acetylhydrolase levels and an important component in minimizing PAF-mediated pathophysiology in livers exposed to endotoxemia.

2.P.337 Secretion of PAF-acetylhydrolase activity during platelet aggregation in patients undergoing coronary angioplasty

2.P.337 Secretion of PAF-acetylhydrolase activity during platelet aggregation in patients undergoing coronary angioplasty

Partial purification and localization of platelet-activating factor acetylhydrolase from bovine seminal plasma.

Platelet-activating factor (PAF) is a potent lipid mediator that is inactivated by platelet-activating factor acetylhydrolase (PAF-AH). Platelet-activating factor bioactivity has been detected in bovine sperm phospholipids and PAF-AH activity is extraordinarily high in bovine seminal plasma. The purpose of this study was to purify and characterize partially the PAF-AH in bovine seminal plasma. Platelet-activating factor acetylhydrolase was partially purified from bovine seminal plasma using gelatin-agarose and ion-exchange chromatography and nondenaturing polyacrylamide gel electrophoresis (PAGE). Enzyme activity was increased 11-fold over seminal plasma with a yield of 11%. Platelet-activating factor acetylhydrolase activity was eluted from a single band with a R(f) of 0.258 from a nondenaturing preparative PAGE gel along with several other proteins of varying molecular weights. Following separation by sodium dodecyl sulfate (SDS)-PAGE under reducing conditions, PAF-AH was identified as a approximately 60-kD band by western blotting using antiserum directed against human blood PAF-AH. N-terminal sequencing of the approximately 60 kD band, followed by amino acid-sequence similarity searching, demonstrated a single-sequence match with PAF-AH from bovine blood. Based on western blotting, a approximately 60-kD band corresponding to PAF-AH was detected in seminal vesicle fluid but not in samples of washed, sonicated sperm or sperm plasma membranes where activity was low (<5% and <0.3%, respectively, of that in seminal plasma), suggesting that seminal plasma PAF-AH does not bind tightly to sperm. Specific PAF-AH activity measured in seminal vesicle fluid was in the lower range of that in seminal plasma. These results demonstrate that PAF-AH activity in bovine seminal plasma is due to PAF-AH secreted by the seminal vesicles with sequence homology to the enzyme in human blood.

Activated Mast Cells Release Extracellular Type Platelet-activating Factor Acetylhydrolase That Contributes to Autocrine Inactivation of Platelet-activating Factor

IgE-dependent and -independent activation of mouse bone marrow-derived mast cells (BMMC) elicited rapid and transient production of platelet-activating factor (PAF), which reached a maximal level by 2-5 min and was then degraded rapidly, returning to base-line levels by 10-20 min. Inactivation of PAF was preceded by the release of PAF acetylhydrolase (PAF-AH) activity, which reached a plateau by 3-5 min and paralleled the release of beta-hexosaminidase, a marker of mast cell exocytosis. Immunochemical and molecular biological studies revealed that the PAF-AH released from activated mast cells was identical to the plasma-type isoform. In support of the autocrine action of exocytosed PAF-AH, adding exogenous recombinant plasma-type PAF-AH markedly reduced PAF accumulation in activated BMMC. Furthermore, culture of BMMC with a combination of c-kit ligand, interleukin-1beta and interleukin-10 for > 24 h led to an increase in plasma-type PAF-AH expression, accompanied by a reduction in stimulus-initiated PAF production. Collectively, these results suggest that plasma-type PAF-AH released from activated mast cells sequesters proinflammatory PAF produced by these cells, thereby revealing an intriguing anti-inflammatory aspect of mast cells.

Platelet-activating factor in plasma of patients with sickle cell disease in steady state

The role of platelet-activating factor (PAF) in the pathogenesis of microvascular vaso-occlusion in sickle cell disease (SCD) is not known. In order to assess a role for PAF in vaso-occlusion in patients with SCD in steady state conditions, we measured plasma PAF level and plasma PAF acetylhydrolase activity as indices of PAF metabolism in vivo. We also studied PAF synthesis, from ( 3H)-acetate, by purified platelets stimulated with A23187. PAF was extracted from plasma of ten patients with SCD in steady state and from age-matched controls. PAF, purified by thin-layer chromatography, was quantitated by radioimmunoassay. PAF level (mean ± SEM, pg/ml) in plasma of controls was 393 ± 65, which was significantly lower than the 797 ± 62 measured in plasma of patients with SCD. There was no difference in acetylhydrolase activity between the two groups. PAF synthesis (mean ± SEM, nmol/ 10 6 cells) by platelets of controls without exogenous lyso-PAF was 1.69 ± 0.24, higher than the 0.59 ± 0.038 synthesized by platelets of patients with SCD. Incubation of platelets with 1.0 μmol/L lyso-PAF increased PAF synthesis by controls to 8.93 ± 1.76, still higher than the 4.59 ± 0.98 synthesized by platelets of patients with SCD. Our data show that patients with SCD are susceptible to a higher circulating levels of PAF in vivo during steady-state conditions. We speculate that higher levels of PAF may be a contributing factor to the persistent stress and inflammatory state of the microcirculation of patients with SCD.

Increased activity of platelet-activating factor acetylhydrolase in low-density lipoprotein subfractions induces enhanced lysophosphatidylcholine production during oxidation in patients with heterozygous familial hypercholesterolaemia.

Patients with heterozygous familial hypercholesterolaemia (FH) have elevated plasma concentrations of low-density lipoprotein (LDL) and develop premature atherosclerosis. There is increasing evidence that oxidative modification of LDL is important for the pathogenesis of atherosclerosis, and the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the distribution of PAF-AH activity among three LDL subfractions isolated by gradient ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic control subjects. We also determined the lyso-PC production in each LDL subfraction during Cu2(+)-induced oxidation in vitro. The total serum PAF-AH activity in heterozygous FH patients was significantly higher than in control subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage of total serum PAF-AH activity, was significantly lower in the FH patients than in control subjects (13.9 +/- 6.6% vs. 30.6 +/- 4.4%, P < 0.001). Among the LDL subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH patients, expressed as nmol mg-1 protein min-1, was significantly higher in the LDL3 subfraction (33.1 +/- 4.8 and 53.4 +/- 11.5 respectively) than in the LDL2 (18.6 +/- 5.3 and 26.8 +/- 10.4 respectively, P < 0.0001 for both comparisons) and LDL1 subfractions (5.1 +/- 1.5 and 7.8 +/- 2.6, respectively, P < 0.0001 for both comparisons). Additionally, the enzyme activity in each LDL subfraction of the heterozygous FH patients was significantly higher than in control subjects (P < 0.02 for LDL1, P < 0.03 for LDL2 and P < 0.0001 for LDL3). No difference was observed in the susceptibility to oxidation of each LDL subfraction among the heterozygous FH patients and the normolipidaemic control subjects. During oxidation, the PAF-AH activity decreased, whereas the lyso-PC levels significantly increased in all subfractions of both groups. The lyso-PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after the onset of the oxidation was significantly higher than in control subjects [0.38 +/- 0.05 and 0.27 +/- 0.04, respectively, for LDL1 (P < 0.006), 0.47 +/- 0.08 and 0.39 +/- 0.03, respectively, for LDL2 (P < 0.04), 0.55 +/- 0.11 and 0.42 +/- 0.06, respectively, for LDL3 (P < 0.02)]. Our results show that heterozygous FH patients exhibit higher PAF-AH activity than control subjects in all LDL subfractions, resulting in higher lyso-PC production during oxidation, which confers on these subfractions higher biological potency. This phenomenon, in combination with the diminished anti-atherogenic and antioxidant capability of HDL in these patients due to the relatively low HDL-cholesterol levels compared with LDL-cholesterol levels and, consequently, the relatively low HDL-associated PAF-AH activity, could contribute to the higher atherogenicity and incidence of coronary artery disease observed in FH patients.

PLATELETS INHIBIT THE ACTIVITY OF PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IN MONOCYTE-DERIVED MACROPHAGES

Blood platelets are capable of interacting with monocytes and macrophages and of enhancing various functions of these cells, which are believed to play a role in thrombosis and inflammation. An increase in the uptake of oxidised low density lipoprotein (LDL), in the synthesis of procoagulant tissue factor, thrombospondin and leukotrienes, as well as stimulation of oxygen radical production by platelets has been described (1-5). In circulating blood, a substantial proportion of monocytes was found to be associated with platelets, but the pathophysiological significance of such platelet-monocyte conjugates is not yet clear (6,7). Immigration of monocytes into the arterial intima and their differentiation into macrophages are initial steps in the development of an atherosclerotic lesion (8). During differentiation, there is a tremendous increase in the activity and secretion of the enzyme PAF acetylhydrolase (PAF = platelet-activating factor = 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) (9,10), and there is some evidence that this enzyme may contribute to the development of atherosclerosis. It cleaves PAF, and the remaining lyso-PAF is chemotactic for monocytes (11). Furthermore it also acts on oxidised low density lipoproteins and enhances their uptake into macrophages (12,13). We were therefore interested in investigating whether platelets may modulate the differentiation of monocytes into macrophages and the activity of PAF acetylhydrolase.

Novel Function of Lecithin-Cholesterol Acyltransferase: HYDROLYSIS OF OXIDIZED POLAR PHOSPHOLIPIDS GENERATED DURING LIPOPROTEIN OXIDATION

Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

102 Increased activity of PAF-acetylhydrolase in low density lipoprotein subfractions induces enchanced lysophosphatidylcholine production in patients with heterozygous familial hypercholesterolemia

102 Increased activity of PAF-acetylhydrolase in low density lipoprotein subfractions induces enchanced lysophosphatidylcholine production in patients with heterozygous familial hypercholesterolemia

Platelet-activating factor (PAF) and PAF acetylhydrolase activity in rat uterus and placenta during the late stages of pregnancy.

We evaluated the roles of platelet-activating factor (PAF) and PAF-acetylhydrolase (PAF-AH) activity in late pregnancy. Uterine and placental concentrations of PAF were determined by the washed rabbit platelet aggregation bioassay. Uterine, placental, and plasma PAF-AH activities were also assayed. PAF concentration in the uterus increased 4-fold between Days 15 and 21 of pregnancy. PAF was also determined in the placenta on Days 15 and 21. In contrast to findings in the uterus, the concentration in the placenta was decreased by 75%. Platelet aggregation caused by uterine and placental PAF was inhibited by the PAF receptor antagonists CV-3988 and TCV-309. Plasma and uterine PAF-AH activities decreased significantly between Days 15 and 21. In contrast, the placental PAF-AH activity significantly increased during this same time period. On the basis of these findings, it is suggested that the PAF concentration in the uterus and placenta may be regulated by intracellular PAF-AH and/or plasma PAF-AH activities. Increased PAF activity in the pregnant rat uterus may be related to the initiation of labor due to its known effect on myometrial contraction. Decreased PAF concentration in the placenta may contribute to the fetoplacental circulation due to its known hypotensive activity and the increase in vascular permeability.