Endothelial cells for studies of platelet-activating factor and arachidonate metabolites.
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Animals↗
Biomedical subjects
S M Prescott
Publications and source records attributed to S M Prescott.
Lipid metabolism and signal transduction in endothelial cells.
Endothelial cells have the capacity to metabolize several important lipids; this includes the ability to store and then metabolize arachidonate, as well as the capacity to synthesize platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). Arachidonate is predominantly metabolized via cyclooxygenase to PGI2 although the spectrum of prostaglandins may vary depending upon the source of the endothelial cell. Biosynthesis of eicosanoids and PAF are likely to be an important physiologic function of the endothelial cell as these potent lipids appear to have a role in maintaining vascular tone and mediating interactions of the endothelium with circulating inflammatory cells. In addition to production of eicosanoids and PAF, endothelial cells metabolize exogenous arachidonate and arachidonate metabolites and other fatty acids such as linoleate to bioactive compounds (HODEs). There is also evidence that small amounts of arachidonate are metabolized via a lipoxygenase. The physiologic significance of these minor lipid pathways is not known at this time. Production of eicosanoids and PAF is not a constitutive function of the endothelial cell. Lipid biosynthesis by endothelial cells is one component of the early activation response that occurs in response to stimulation with pro-inflammatory and vasoactive hormones or to pathologic agents such as oxidants and bacterial toxins. A central mechanism for activation of the relevant pathways is a rise in cellular calcium concentrations that can be mediated by hormone-receptor-binding or by direct permeabilization of the cell membrane to calcium (Fig. 3). Regulatory mechanisms distal to the calcium signal are unknown, but current evidence suggests that calcium directly or indirectly activates phospholipases that release arachidonate from phospholipids and hydrolyze a specific phospholipid to the immediate precursor of PAF. There is evidence that protein kinase C may, in part, regulate this process, but the role of other potential regulatory components, such as other protein kinases or G-proteins is not known. As noted above, the most direct mechanism for initiation of PAF biosynthesis and arachidonate release would be activation of a phospholipase A2 as shown in Fig. 3. Activation of other phospholipases (e.g. phospholipase C) may contribute to the total amount of arachidonate released, although the magnitude of that contribution is not yet known. In addition to generation of PAF and eicosanoids, activation of endothelial cell phospholipases generates second messengers that are important in intracellular signaling (Fig. 4). Activation of phospholipase C, in response to hormonal stimulation, generates diacylglycerol and inositol phosphates from phosphatidylinositol. Each of these is a potent intracellular second messenger.(ABSTRACT TRUNCATED AT 400 WORDS)
Arachidonic Acid↗
Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion.
The binding of neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial cells (ECs) presents special requirements in the regulation of intercellular adhesion. ECs that are stimulated by certain agonists, including thrombin and cytokines (tumor necrosis factor alpha, interleukin-1), generate molecular signals that induce the adhesion of PMNs (endothelial cell-dependent neutrophil adhesion). Our experiments demonstrate that the mechanism of binding induced by thrombin is distinct from that induced by the cytokines based on the time courses, the requirement for protein synthesis, and differential binding of HL60 promyelocytic leukemia cells to ECs activated by the two classes of agonists. The rapid EC-dependent PMN adhesion (initiated in minutes) that occurs when the ECs are stimulated by thrombin is temporally coupled with the accumulation of platelet-activating factor, a biologically active phosphoglyceride that remains associated with ECs and that activates PMNs by binding to a cell surface receptor. A portion of the newly synthesized platelet-activating factor (PAF) is on the EC surface, as demonstrated by experiments in which the rate of hydrolysis of PAF synthesized by activated ECs was accelerated by extracellular PAF acetylhydrolase. When ECs were treated with exogenous PAF they became adhesive for PMNs; the PMN binding was prevented by incubating the ECs with PAF acetylhydrolase or by treating the PMNs with competitive PAF receptor antagonists. Thus PAF associated with the EC plasma membrane induces PMN binding, an observation supported by experiments in which PAF in model membranes (liposomes) stimulated rapid PMN adhesion to ECs and to cell-free surfaces. In addition, competitive antagonists of the PAF receptor inhibited the binding of PMNs to ECs activated by thrombin and other rapidly acting agonists, but not to ECs activated by tumor necrosis factor alpha, indicating that PAF that is endogenously synthesized by ECs can mediate neutrophil adhesion. These experiments demonstrate a novel mechanism by which a cell-associated phospholipid, PAF, can serve as a signal for an intercellular adhesive event.
Biological Factors↗
Brief review: molecular mechanisms of neutrophil binding to endothelium involving platelet-activating factor and cytokines.
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Antigens, CD↗
Phospholipid remodeling in human neutrophils. Parallel activation of a deacylation/reacylation cycle and platelet-activating factor synthesis.
A23187 stimulated two enzymatic activities of human neutrophils (polymorphonuclear leukocytes), phospholipase A2 and fatty acyl-CoA acyltransferase, which resulted in a stimulated deacylation/reacylation cycle. The incorporation of fatty acids, other than arachidonic or eicosapentaenoic acid, into diacyl and alkylacyl species of choline phosphoglycerides was stimulated by 10-fold by A23187. These fatty acids were exclusively incorporated into the sn-2 position, and [3H]glycerol labeling showed there was no stimulation of de novo synthesis. A23187 also stimulated fatty acid incorporation into other phospholipids, but de novo synthesis accounted for a portion of this uptake. Inhibitors of protein kinase C prevented the stimulated recycling of phosphatidylcholine, and the simultaneous induction of platelet-activating factor synthesis, by inhibiting phospholipase A2 activation. They inhibited [3H]arachidonate release from prelabeled polymorphonuclear leukocytes, but had no effect on in vitro fatty acyl-CoA acyltransferase or acetyl-CoA acetyltransferase activity. Extracts from A23187-treated cells contained a fatty acyl-CoA acyltransferase, which did not utilize arachidonoyl-CoA, that was 2.3-fold more active than that of control extracts. Phosphatase treatment decreased this stimulated activity by 66%. Thus, A23187 stimulated a phospholipase A2 activity that generated both 1-alkyl and 1-acyl lysophosphatidylcholines. A stimulated acetyltransferase used a portion of the alkyl species for platelet-activating factor synthesis, while the acyl species and residual alkyl species were rapidly reacylated to phosphatidylcholine by a stimulated acyl-transferase. Arachidonate, an eicosanoid precursor, was spared by this process.
Acylation↗
Neutrophil activating factor (NAF) induces polymorphonuclear leukocyte adherence to endothelial cells and to subendothelial matrix proteins.
Neutrophil activating factor is a polypeptide cytokine released from stimulated mononuclear phagocytes and endothelial cells. We found that neutrophil activating factor induced time- and concentration-dependent binding of human polymorphonuclear leukocytes to endothelial monolayers and subendothelial matrix proteins, via a mechanism that involves altered expression of the leukocyte CD11/CD18 glycoproteins. Thus, neutrophil activating factor is a third mediator, in addition to platelet-activating factor and endothelial leukocyte adhesion molecule 1, that is synthesized by activated endothelium and that can induce polymorphonuclear leukocyte adhesion to endothelial cells. Because NAF is released into the pericellular fluid, it may also stimulate binding of the leukocytes to exposed subendothelial structures at sites of vascular injury.
Antigens, Surface↗
Platelet-activating factor acetylhydrolase increases during macrophage differentiation. A novel mechanism that regulates accumulation of platelet-activating factor.
Monocytes and macrophages produce bioactive lipids, such as platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF), that mediate inflammation. These cells synthesize PAF following their activation, but not constitutively. Previous studies have demonstrated that PAF accumulation is regulated by the activity of the synthetic enzymes. We observed that the accumulation of PAF in stimulated human monocytes decreased by 90% as they differentiated into macrophages. There was no decrease in the activities of the synthetic enzymes; however, the activity of the degradative enzyme, PAF acetylhydrolase, increased 260-fold. The increase in PAF acetylhydrolase activity appeared to result from a net increase in the synthesis of a new enzyme. These studies demonstrate a novel mechanism in which an increase of the degradative enzyme regulates the accumulation of PAF. This may be an important mechanism by which macrophages modulate inflammatory responses.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
The regulation of platelet-activating factor production in endothelial cells. The role of calcium and protein kinase C.
Endothelial cells (EC) synthesize platelet-activating factor (PAF) when stimulated with agonists that bind to cell-surface receptors. We examined events that link receptor binding to synthesis of PAF by EC. Bovine EC stimulated with agonists that interact with specific cell-surface receptors accumulated PAF only in the presence of extracellular calcium. Hormonal stimulation of EC resulted in Ca2+ entry characteristic of that seen with receptor-operated calcium channels; Indo-1 measurements demonstrated that this inward flux of Ca2+ caused prolonged elevated levels of intracellular Ca2+. EC were exposed to melittin or theta toxin from Clostridium perfringens (pore-forming peptides that increase the permeability of the plasma membrane for small molecules) resulting in an inward flux of Ca2+ and accumulation of PAF. Ca2+ appears to be regulatory for PAF production at the level of phospholipase A2-mediated production of the PAF precursor 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine, as Ca2+ was required for the stimulated hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine. PAF accumulation in EC is also regulated by protein kinase C. Pretreatment of EC with phorbol esters that activate protein kinase C or with dioctanoylglycerol, followed by stimulation, resulted in a 2-fold increase in stimulated PAF production. The regulatory effect of protein kinase C also appears to be at a phospholipase A2-mediated hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine.
Adenine Nucleotides↗
An oxidized derivative of phosphatidylcholine is a substrate for the platelet-activating factor acetylhydrolase from human plasma.
Platelet-activating factor (PAF) is a glycerophospholipid that has diverse potent biological actions. A plasma enzyme catalyzes the hydrolysis of the sn-2 acetoyl group of PAF and thereby abolishes its bioactivity. This PAF acetylhydrolase is specific for phospholipids, such as PAF, with a short acyl group at the sn-2 position. The majority of it (60-70%) is associated with low density lipoprotein (LDL), and the remainder is with high density lipoprotein (HDL). LDL also has a phospholipase A2 activity that is specific for oxidized polyunsaturated fatty acids, which may be important in determining how LDL is recognized by cellular receptors. We previously have purified and characterized the PAF acetylhydrolase from human plasma. We now have found that the purified PAF acetylhydrolase catalyzes the hydrolysis of the oxidized fragments of arachidonic acid from the sn-2 position of phosphatidylcholine. One of the preferred substrates appeared by mass spectrometry to have 5-oxovalerate at the sn-2 position. We synthesized 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine and found that the PAF acetylhydrolase had the same apparent Km for it (11.3 microM) as for PAF (12.5 microM), with Vmax values of 100 and 167 mumol/h/mg of protein, respectively. We also conclude that the PAF acetylhydrolase is the sole activity in LDL that degrades oxidized phospholipids since we found co-localization of the activity against both substrates to LDL and HDL, and precipitation of enzyme activity with an antibody to the PAF acetylhydrolase. Thus, the PAF acetylhydrolase in human plasma degrades oxidized phospholipids, which may be involved in the modification of apolipoprotein B100 and other pathological processes.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.
Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Arachidonate metabolism in cultured fibroblasts derived from normal and infarcted canine heart.
Metabolites of arachidonic acid (eicosanoids) may have an important role in the healing process after myocardial infarction. We examined the ability of cardiac fibroblasts from normal and from healing infarcted ventricle to metabolize arachidonate. We induced myocardial infarction in dogs and then allowed them to recover for 1 week, at which time they were killed, and the heart was removed. Fibroblasts were harvested from normal and from the healing, infarcted areas of the left ventricle. The cells from each source were morphologically indistinguishable. There were 347 +/- 102-fold more fibroblasts cultured from the infarcted area than from the normal area. Interestingly, the infarct-derived cells had a slower doubling time (37.4 +/- 3.7 hours) than the normal cells (22.0 +/- 3.6 hours). The uptake of exogenous arachidonate and its distribution in complex lipids was the same in the cells from each area. When stimulated with the calcium ionophore, free exogenous arachidonate, bradykinin, or histamine the cells produced prostaglandin E2 and prostaglandin I2. In each case the infarct-derived cells produced from twofold to fivefold more prostaglandin than the normal cells. We also found that prostaglandin synthesis was highly dependent on the growth state of the cells with a marked decrease a confluence. Finally, in experiments designed to mimic the early state of infarction, we confirmed that isolated cardiac myocytes release arachidonate and showed that normal fibroblasts can incorporate it. The production of eicosanoids by cardiac fibroblasts may be substantial during the healing of myocardial infarction due to their dramatic proliferation and the increased prostaglandin production per cell.
Animals↗
Synthesis and release of platelet-activating factor by stimulated human mononuclear phagocytes.
Platelet-activating factor (PAF) is a potent phospholipid mediator that may participate in inflammatory responses by virtue of its ability to activate platelets, leukocytes, and vascular cells. We examined the synthesis and release of PAF by human peripheral blood monocytes (PBM) isolated by countercurrent elutriation. PAF was produced after stimulation by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and PMA with a relative order of potency IoA much greater than OpsZ greater than PMA. The portion of PAF subsequently released from the cell was dependent on the specific agonist, the time of incubation, and the presence of albumin. Under optimal conditions, PBM released 67, 49 and 32% of the total PAF produced in response to IoA, OpsZ, and PMA, respectively. Changes in PAF metabolism were observed in PBM that were examined after short term adherence or differentiation into macrophages. Adherent PBM accumulated and released less PAF than suspended monocytes, and monocyte-derived macrophages produced less PAF than the parent PBM. The ability of monocytes to release significant amounts of newly synthesized PAF from the cell is unusual among human cell types, which in general retain the vast majority of the lipid, and may be of particular pathophysiologic importance.
Calcimycin↗
Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion.
Oxidant-induced damage to the intima of pulmonary and systemic vessels is thought to be an important mechanism of injury in a variety of syndromes of vascular damage. Hydrogen peroxide (H2O2) is an active oxygen metabolite that may induce intimal injury by cytolytic attack or by inducing biochemical and functional alterations in the endothelial cells (EC); however, mechanisms involved in noncytolytic perturbation of EC are largely unknown. We found that H2O2 stimulated the synthesis of platelet-activating factor (PAF) by primary cultures of bovine pulmonary artery endothelium (BPAEC) and by human umbilical vein endothelium (HUVEC). In each cell type the incorporation of [3H]acetate into [3H-acetyl]PAF was concentration- and time-dependent and was temporally dissociated from severe plasma membrane disruption and cytolytic cell injury; the newly synthesized PAF remained associated with the EC. H2O2 caused permeabilization of EC to 45Ca2+ and an increase in intracellular Ca2+, suggesting that a transmembrane Ca2+ flux is the signal that initiates PAF synthesis. H2O2 also induced the endothelial cell-dependent adhesion of neutrophils to HUVEC monolayers. This response was rapid, with an onset within minutes and a subsequent time course that paralleled the time course of PAF accumulation, and was dependent on extracellular Ca2+ but not on de novo protein synthesis. These studies demonstrate that H2O2 can induce two rapid activation responses of endothelium, PAF synthesis and EC-dependent neutrophil adhesion, events that may be important in physiologic and pathologic inflammation.
Animals↗
The regulation of synthesis of platelet-activating factor by endothelial cells.
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Animals↗
Protein kinase C activity appears to be required for the synthesis of platelet-activating factor and leukotriene B4 by human neutrophils.
Human neutrophils synthesize platelet-activating factor (PAF) and leukotriene B4 (LTB4) when stimulated with the Ca2+ ionophore A23187. These processes are enhanced to a variable extent by phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C. The long chain amines sphingosine, stearylamine (Hannun, Y.A., Loomis, C.R., Merrill, A.H., Jr., and Bell, R.M. (1986) J. Biol. Chem. 261, 12604-12609), and palmitoylcarnitine competitively inhibit activation of purified protein kinase C in vitro and inhibit protein kinase C-mediated activation of the respiratory burst in human neutrophils (Wilson, E., Olcott, M.C., Bell, R.M., Merrill, A.H., Jr., and Lambeth, J.D. (1986) J. Biol. Chem. 261, 12616-12623). These amines were found to inhibit A23187-induced PAF and LTB4 synthesis. Inhibition of PAF and LTB4 synthesis occurred in parallel; half-maximal inhibition by sphingosine occurred at 7 microM, with complete inhibition at 15 microM. PMA by itself did not induce the synthesis of PAF or LTB4, although it did enhance PAF and LTB4 synthesis at suboptimal concentrations of A23187. PMA reversed long chain amine inhibition of PAF and LTB4 accumulation. Reversal of the inhibition of PAF and LTB4 accumulation occurred in parallel, was concentration-dependent, and was complete by approximately 3 x 10(-8) M PMA. The inactive 4 alpha-phorbol didecanoate ester did not reverse inhibition at these concentrations. Sphingosine completely prevented the A23187-induced release of [3H]arachidonate and its various metabolites from [3H]arachidonate-labeled cells. PMA, but not 4 alpha-phorbol didecanoate, restored arachidonate release and its metabolism. Therefore, while activation of protein kinase C is not sufficient to induce PAF and LTB4 synthesis, its action appears to be required to couple a rise in intracellular Ca2+ to their synthesis. This coupling occurs at the level of the initial reaction in the production of lipid mediators, a phospholipase A2-like activity that mobilizes the two substrates 1-O-alkyl-sn-glycero-3-phosphocholine and arachidonic acid from complex lipids.
Amines↗
Culture of mesothelial cells from bovine pericardium and characterization of their arachidonate metabolism.
Cultures of mesothelial cells from bovine pericardium were established and their arachidonate metabolism was characterized. The identification of the cultured cells was based on morphological observations, and by electrophoretic analysis of cytoskeletal proteins, which demonstrated a pattern previously reported for mesothelial cells. Factor VIII-related antigen was present by indirect immunofluorescence, but the cells had no thrombomodulin activity. The cultured pericardial cells metabolized arachidonic acid to 6-ketoprostaglandin F1 alpha and a small amount of prostaglandin E2. The same metabolites were produced by pieces of intact parietal pericardium but not by pieces from which mesothelium had been removed. The cultured mesothelial cells produced 94.6 +/- 60.4 (mean +/- S.D.) ng/mg (n = 3) cell protein of 6-ketoprostaglandin F1 alpha in response to the calcium ionophore A23187, 117.3 +/- 13.6 ng/mg (n = 3) with exogenous arachidonic acid, 18.3 +/- 11.3 ng/mg (n = 5) with bradykinin, 8.4 +/- 4.3 ng/kg (n = 4) with histamine and 11.2 +/- 9.7 ng/mg (n = 5) with thrombin. All of these values were significantly higher (P less than 0.05) than the control (2.1 +/- 1 ng/mg; n = 5). From these results, we conclude that the mesothelial cells account for the arachidonate metabolism in the pericardium. The production of prostaglandin I2 occurs in response to physiological or pathological, agonists, and is substantial. That is, it is approximately the same as endothelial cells. The release of eicosanoids by mesothelial cells into the pericardial space may have a significant role in cardiac physiology and pathology.
Animals↗
Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes. Correlation of synthesis with release, functional events, and leukotriene B4 metabolism.
Platelet-activating factor (PAF) is a phospholipid mediator of inflammation that is synthesized by several human cell types including polymorphonuclear leukocytes (PMN). We examined the synthesis and release of PAF by stimulated human PMN under several conditions, assayed by the incorporation of [3H]acetate into PAF and by bioassay. PAF synthesis was induced by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and N-formyl-methionyl-leucyl-phenylalanine (FMLP) with the relative order of potency IoA much greater than OpsZ greater than FMLP. A variety of other agonists, including phorbol myristate acetate, an activator of protein kinase C and of PMN functional responses, did not stimulate PAF synthesis. PAF synthesis by PMN in response to IoA, OpsZ, and FMLP was concentration- and time-dependent but release of the phospholipid was not: little PAF (1 to 10%) was released from PMN in suspension regardless of the total amount produced, the agonist, its concentration, the time of incubation, or the concentration of extracellular albumin. This was also the case with functionally altered neutrophils that had been "primed" with cytochalasin B or lipopolysaccharide or that had adhered to surfaces. PAF synthesis was tightly coupled with leukotriene B4 production by adherent PMN as well as by neutrophils in suspension, supporting the hypothesis that the two lipid autacoids may be derived from a common precursor. However, PAF synthesis could be dissociated from aggregation and surface adhesion, indicating that it is not absolutely required for these responses of activated PMN. The total amount of PAF that accumulated, but not the percentage that was released, was altered in adherent PMN compared to cells in suspension. These experiments demonstrate that PAF production and its subsequent processing by human neutrophils are highly regulated events. PAF synthesis is associated with PMN activation, but it is not a requisite for early adhesive responses of neutrophils. Because little of the PAF produced by stimulated PMN is released from the cells, it appears that PAF has an intracellular role in PMN function and/or that it may have novel intercellular effects that do not require release into the fluid phase.
Calcimycin↗
Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.
Platelet-activating factor (PAF) is a bioactive phospholipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) synthesized by a variety of mammalian cell types. PAF induces hypotension, and activates neutrophils and platelets, among other actions. Removal of the acetyl moiety abolishes biological activity, so this reaction may regulate the concentration of PAF and its physiological effects. We have studied the significance of this reaction, which is catalyzed in vitro by an acetylhydrolase present in mammalian plasma, blood cells, and tissues. We have shown that the plasma PAF-acetylhydrolase is responsible for the degradation of PAF in whole human blood and that alternate pathways for PAF degradation in plasma or blood cells are negligible. Human plasma PAF-acetylhydrolase is associated with low and high density lipoproteins (LDL and HDL with apoE). We have confirmed that the activity is a stable component of these particles by density gradient ultracentrifugation, chromatography on heparin-agarose, and immunoprecipitation. The LDL-associated activity accounts for most or all of the PAF degradation that occurs in plasma ex vivo, while the HDL-associated activity contributes little to this process. However, the two activities likely are due to a single protein since the HDL- and LDL-associated PAF-acetylhydrolase activities can transfer from one lipoprotein to the other. These transfer processes are pH-dependent and specific, since they only occur from LDL to a well characterized subclass of HDL (apoE-containing HDL) and vice versa. We discuss the equilibrium between the two particles and the role that this process may have in vivo.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗