Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Platelet-Activating Factor Acetylhydrolase (Pafah)

  • Gopal Kedihithlu Marathe
  • Shancy Petsel Jacob
  • Mosale Seetharam Sumanth
  • Chikkamenahalli Lakshminarayana Lakshmikanth
  • Kandahalli Venkataranganayaka Abhilash
  • Vyala Hanumanthareddy Chaithra
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101737


Historical Background

Platelet activating factor-acetylhydrolases (PAF-AH) (EC are essentially phospholipase A2 isoenzymes (Group VII and VIII) catalyzing the hydrolysis of short chain acyl group at the second position of phospholipids. An important bioactive lipid that led to the discovery of PAF-AH is platelet-activating factor (PAF), a potent proinflammatory lipid, whose discovery in the early 1970s was a breakthrough that opened a new dimension to the role of phospholipids, until then they were only considered as structural constituents of biological membranes/lipoproteins or at the most precursor for the biologically active phosphoinositides and eicosanoids (Hanahan 1986; Prescott et al. 2000). In 1970, Henson and colleagues (Henson 1970) first proposed the presence of a fluid phase mediator released by sensitized rabbit leukocytes capable of activating platelets and was later identified to be a phospholipid capable of inducing anaphylactic shock (Hanahan 1986). Simultaneously, an antihypertensive polar renal medullar lipid (APRL) displaying properties similar to PAF was shown. Studies in the subsequent years by different research groups focused on the structure of PAF and finally Hanahan et al. deduced its structure as 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (reviewed in Hanahan 1986) (Fig. 1). The prime importance of the acetyl group at the sn-2 position for biological activities of PAF which had a very short half-life of ≈30 sec and its ability to exert a short-term hypotensive effect similar to APRL, suggesting it to be rapidly degraded in the body was shown (Blank et al. 1979). In the following year, Farr et al. (1983) identified an acid-labile factor associated with lipoproteins in serum that could inactivate PAF. This led to the identification of a specific acetylhydrolase capable of inactivating PAF and until then, acetylhydrolases that can utilize phospholipids as substrates were not described. Almost a decade later, acetylhydrolase activity was also found to be present in the cytosolic fractions of various rat tissues such as kidney, lung, spleen, brain, heart, liver (Blank et al. 1981), and in human blood cells (Lee et al. 1982). Unlike other phospholipase A2s, PAF-AH was found to be Ca2+ independent, specific for phospholipids with short acyl group at sn-2 position and shown to be sensitive to serine protease inhibitors (Prescott et al. 2000). In 1987, Stafforini and her colleagues (Stafforini et al. 1987) for the first time purified and characterized PAF-AH from human low density lipoprotein (LDL) using conventional chromatographic techniques and observed that a majority (two-thirds) of the plasma PAF-AH to be associated with LDL, remaining with high density lipoprotein (HDL) and other lipoproteins (Stafforini et al. 1987; Prescott et al. 2000).
Platelet-Activating Factor Acetylhydrolase (Pafah), Fig. 1

Action of PAF-AH on PAF and PAF-like lipids. PAF-AH is essentially a calcium-independent PLA2, which cleaves the ester linkage at the sn-2 position to release biologically inactive lysoPAF and acetate in case of alkyl PAF hydrolysis and Lyso PC and acetate in case of acyl PAF (a); PAF-AH also acts on PAF-like lipids in the same fashion as that of PAF (b)

By this time, parallel investigations were also carried out on the synthesis of PAF by agonist stimulated inflammatory cells such as monocytes and macrophages and nonimmune cells such as endothelial cells (Prescott et al. 2000). While studying the regulation of synthesized PAF, Elstad and coworkers (Elstad et al. 1989) observed that the accumulation of PAF greatly decreased in stimulated human monocytes differentiating into macrophages. This decrease was a result of a 260-fold increase in PAF-AH activity without any decrease in the activities of synthetic enzymes and thus a novel degradative mechanism for regulating levels of PAF by PAF-AH in mature macrophages was defined. In the same year it was reported that plasma PAF-AH could efficiently hydrolyze oxidized fragments of arachidonic acid from sn-2 position of phosphatidylcholines, showing its relaxed range of substrate specificity (reviewed in McIntyre et al. 2009). Subsequently, it was demonstrated that macrophages secreted PAF-AH into plasma and were the cellular source of plasma PAF-AH (reviewed in Stafforini 2009). Apart from plasma, PAF-AH activity was also identified intracellularly in various tissues. Therefore, it became apparent that at least two forms of PAF-AH (one intracellular and one plasma form) exist and both forms show similar characteristics of Ca2+ independency and preference to hydrolyze phospholipids with short sn-2 residues or oxidized residues, but they differed in their gene structure since they are encoded by different genes (Prescott et al. 2000).

The involvement of PAF-AH in pathological responses was recognized when decreased plasma PAF-AH activity, and high levels of PAF was observed in patients with asthma, systemic lupus erythematosus, and septic shock (reviewed in Stafforini 2009a; Marathe et al. 2014). In 1995, Tjoelkar et al. (1995) successfully cloned human plasma PAF-AH and demonstrated that the enzyme was a unique serine esterase with an active site residue containing a catalytic triad composed of a serine, an acidic residue (usually aspartate), and a histidine residue – signature residues found in lipases. Further, the recombinant enzyme was found to impart protection against PAF-mediated responses in vivo and in vitro, suggesting that administration of exogenous PAF-AH could be beneficial in pathological conditions where PAF and related compounds accumulate. Over the course of time, PAF-AH has been a subject of extensive research showing its association with a range of inflammatory diseases and till date, one secreted (plasma form) and three intracellular isozymes (PAF-AH, Ib, and II) of PAF-AH have been described in mammals (Prescott et al. 2000; Stafforini 2009a). The localization of these enzymes is however not stringent, since the plasma PAF-AH is also found intracellularly and the intracellular forms of the enzymes are detected in circulation as well (Chen et al. 2007; Zhou et al. 2011; Marathe et al. 2014).

The Plasma PAF Acetylhydrolase

The plasma PAF-AH, now commercially available as pafase (ICOS Corporation, Bothell, WA, USA), belongs to group VII of phospholipase A2 subfamily and is the most abundant and thoroughly characterized enzyme in this family. The gene PLA2G7 is found in thymus, tonsil, and placenta (Stafforini 2009a) and encodes a 440 amino acid long protein. Site-directed mutagenesis has revealed the presence of a typical catalytic triad (Stafforini 2009a) with Ser-273 important for activity since, serine protease inhibitors such as diisopropyl fluorophosphate (DFP), methyl arachidonyl fluorophosphonate (MAFP), and Pefabloc (nontoxic DFP substitute) (Chen et al. 2007) inhibit the enzyme. The human plasma PAF-AH is extensively N-glycosylated with an apparent molecular mass of 45 kDa (Prescott et al. 2000; Marathe et al. 2014) that varies with the extent of glycosylation. Purified human plasma PAF-AH shows an activity (Vmax = 170 μmol/min/mg) sufficient enough to hydrolyze lowest concentrations of PAF and has a Km value greater than the PAF levels found in plasma under physiological and pathological conditions (Stafforini et al. 1987). The principal source of plasma PAF-AH is macrophage, followed by hepatocytes and hematopoietic cells. However, in human subjects deficient in plasma PAF-AH activity receiving allogenic bone marrow transplants, circulating PAF-AH activity correlated with the donor’s genotype, suggesting that hematopoietic cells accounted for the secreted PAF-AH (Stafforini 2009a).

Intracellular PAF Acetylhydrolase

As mentioned earlier, besides plasma PAF-AH, cytosolic fractions of a variety of tissues such as kidney, lung, spleen, brain, heart, and liver are reported to contain at least two isoforms of PAF-AH; Ib and II (Farr et al. 1983; McIntyre et al. 2009). Both the intracellular enzymes belong to group VIII phospholipase A2 subfamily. Among the intracellular PAF-AH, the most thoroughly studied is the isoform Ib, a heterotrimeric enzyme with subunits α, β, and γ of molecular masses of 45, 30, and 29 kDa respectively. The 29 and 30 kDa subunits are catalytically active and contain trypsin-like triad of Ser-His-Asp at the active site with a homology of 63.2% (Hattori et al. 1995). The 45 kDa subunit is catalytically inactive and is involved in the regulation and turnover of the holoenzyme. The loss of the gene encoding the 45 kDa subunit of PAF-AH Ib is associated with Miller-Dieker lissencephaly, a brain malformation syndrome (Matsuzawa et al. 1997). The isoform II (PAF-AH II) is a single polypeptide of 40 kDa with 41% homology with plasma PAF-AH and most abundantly expressed in bovine liver and kidney (Matsuzawa et al. 1997). PAF-AH II is identified to be a myristoylated enzyme distributed in cytosol and membrane fractions. Like plasma PAF-AH, PAF-AH II can hydrolyze PAF and related oxidized phospholipids with short sn-2 residues, whereas PAF-AH Ib behaves as a firm acetylhydrolase specific only for PAF and does not hydrolyze oxidized phospholipids (McIntyre et al. 2009; Matsuzawa et al. 1997). Additionally, PAF-AH from human erythrocytes has been shown to be composed of two identical 25 kDa subunits (Zhou et al. 2011) and recently this intracellular PAF-AH is shown to hydrolyze aspirin in blood (Zhou et al. 2011), while plasma PAF-AH is unable to perform asparin hydrolysis. In recent years, PAF-AH has been recognized to possess additional antioxidant activity, where a yeast PAF-AH ortholog is shown to suppress oxidative death (Foulks et al. 2009; McIntyre et al. 2009).

Substrates for PAF Acetylhydrolase

PAF-AH catalyzes the removal of sn-2 residue of acyl/alkyl PAF to produce acetate and lyso PC/lyso PAF (McIntyre et al. 2009) (Fig. 1). Two important features of PAF-acetylhydrolases that distinguish them from other PLA2 enzymes are (i) lack of Ca2+ requirement and (ii) their marked selectivity for phospholipids with short sn-2 residues with no measurable activity towards intact fatty acids esterified to glycerol, unless they are oxidatively modified as in esterified isoprostanes (Stafforini 2009a; Marathe et al. 2014). Thus, normal cellular phospholipids and lipoproteins are spared from hydrolysis by this actively circulating enzyme in blood (Marathe et al. 2014). Moreover, the presence of an ether (alkyl PAF) or an ester bond (acyl PAF) at the sn-1 position has no influence on the activity of PAF-AH, although the acyl analog is several folds less potent than its alkyl counterpart in activating PAF-R (Marathe et al. 2014). The spectrum of substrates for PAF-AH (except PAF-AH Ib) is thus vastly relaxed with a wide array of related molecules serving as substrates (Fig. 2). In addition to PAF, oxidized phospholipids (OxPLs), including long-chain phospholipid hydroperoxides and PAF-like lipids or PAF-mimetics that can activate the PAF-R with varied potencies to mimic many of the biological effects of PAF can also be hydrolyzed by plasma and type II PAF-AH (Stafforini 2009a; Marathe et al. 2014). Such modified OxPLs are identified to be formed nonenzymatically during oxidative insult and are constituents of oxidized LDLs, including electronegative LDL, alcoholic, smoker’s blood, and in models of cutaneous inflammation (Marathe et al. 2014). Truncated phospholipids that are oxidized products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) such as 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and fragmented products of 1-hexadecyl-2-arachidonoyl-sn-glycero-3-phosphocholine such as butanoyl/ butenoyl analogs of PAF (C4-PAF) also serve as substrates for plasma and type II PAF-AH (Fig. 3) (Prescott et al. 2000; Marathe et al. 2014). The exceptionally extended substrate specificity of PAF-AH thus terminates the inappropriate signaling of OxPLs that are likely to circumvent other cellular controls (Marathe et al. 2014). Hence it is the ability of PAF-AH to curtail the biological potencies of PAF and related lipids, many of which exhibit potent biological actions when they accumulate inappropriately, acquires it to be aptly termed “the signal terminator” of inflammation (Marathe et al. 2014).
Platelet-Activating Factor Acetylhydrolase (Pafah), Fig. 2

Anti-inflammatory properties of PAF-AH. PAF/ PAF-like lipids derived from either oxidized-LDL or membrane phospholipids due to formations of whiskers (Greenberg et al. 2008) exert proinflammatory action. This is blocked by PAF-AH (protein razor) as it cleaves at sn-2 position to produce a biologically inactive lyso PAF and thereby showing anti-inflammatory effects. Recently, presence of intracellular nuclear PAF-R similar to cell surface PAF-R is also documented (Marrache et al. 2002; Bhosale et al. 2016). PAF-like lipids can also be recognized by the scavenger receptor CD36. A putative phospholipid transporter TMEM30 to transport PAF-like lipid across the membrane has also been proposed in some cells (Chen et al. 2011)

Platelet-Activating Factor Acetylhydrolase (Pafah), Fig. 3

Structure of PAF and PAF mimetics. Chemically alky and acyl analog of PAF are structurally very similar except for sn-1 position. Alkyl PAF has a nonhydrolyzable ether linkage while acyl PAF has an ester linkage. PAF-mimetics have variable residues at sn-2 position in both alkyl and acyl series (reviewed in Marathe et al. 2014)

Deficiency of PAF-AH and Inflammatory Diseases

The precise regulation of the concentrations of PAF and related OxPLs in tissues and body fluids is particularly vital to avoid their inappropriate accumulation as observed in many pathological conditions (Marathe et al. 2014). This is achieved by several redundant regulatory mechanisms that include tight regulation of the synthetic pathways, cell-specific expression of its receptor (PAF-R), homologous and heterologous desensitization of the PAF-R, and essentially its rapid clearance and metabolism to an inactive product by PAF-AH. Any impairment in these mechanisms would prolong inflammation and uncalled recruitment of effector cells to sites of injury. Several in vitro and in vivo observations indicate that the signaling triggered by PAF and oxidized PAF-like lipids are effectively abolished by plasma PAF-AH, thus regulating inappropriate inflammation (Prescott et al. 2000; McIntyre et al. 2009; Marathe et al. 2014).

The apparent role for PAF and PAF-AH in a host of inflammatory disorders is well documented, where decreased level of PAF-AH has been observed in a number of diseases such as asthma, coronary heart disease, stroke, systemic lupus erythematosus, sepsis, and Crohn’s disease (reviewed in Marathe et al. 2014). For instance, Graham et al. (1994) observed a 50% decrease in plasma PAF-AH activity in patients with sepsis and showed that the half-life of PAF in the plasma was prolonged in patients with the worst outcomes. Moreover, the administration of exogenous PAF-AH protects animals from undergoing PAF-and antigen-induced anaphylactic shock (McIntyre et al. 2009) and lung inflammation (Henderson et al. 2000). A study by Teixeira-da-Cunha et al. (2013) shows that bacterial clearance is increased in septic mice treated with rPAF-AH. The beneficial role of PAF-AH has also been demonstrated in vitro, where endothelial cells pretreated with PAF-AH were protected from undergoing apoptosis when exposed to oxidized LDL (OxLDL) (Marathe et al. 2014). Also, the deficiency of plasma PAF-AH due to genetic mutation is correlated with severity of several inflammatory conditions including asthma and systemic lupus erythematosus (Stafforini 2009b). Additionally, Stafforini et al. (2009b) has reported the prevalence of a missense mutation (V279F) near the active site of plasma PAF-AH among 4% of Japanese, resulting in loss of activity contributing to an increased risk to develop a range of inflammatory disorders and the homozygous-deficient subjects for this mutation suffered from severe asthma (reviewed in Stafforini 2009b). In addition, several other mutations in the gene encoding plasma PAF-AH have also been observed in different population that are listed in Table 1 (reviewed in Stafforini 2009b).
Platelet-Activating Factor Acetylhydrolase (Pafah), Table 1

Polymorphisms reported in plasma PAF-AH gene and the observed consequences

Type of mutation

Amino acid substitution



Loss of function



Severe asthma, abdominal aortic aneurysm, CVD, CAD, myocardial infarction, stroke, hypertension, cerebral infarction

Loss of function



Asthma, CAD

Neutral mutation



No significant pathological consequences

Neutral mutation



No significant functional consequences

Neutral mutation



Increased sensitization to atopic asthma in German population

Neutral mutation

L12 L

Very rare

Functional consequences unknown

Neutral mutation


Very rare

Functional consequences unknown

Neutral mutation

K191 N

Very rare

Functional consequences unknown

Neutral mutation


Very rare

Functional consequences unknown

CAD coronary artery disease, CHD coronary heart disease, CVD cardiovascular disease

PAF-AH: Marker Versus Risk Factor

Despite evidences favoring the anti-inflammatory potentials of PAF-AH, its credibility as an anti-inflammatory enzyme is a subject of debate. This uncertainty regarding the anti-inflammatory nature of PAF-AH came from the WOSCOPS (West Of Scotland Coronary Prevention Study) in 2000, that documented a positive association of elevated levels of PAF-AH with CVDs (reviewed in Marathe et al. 2014). This correlation led PAF-AH to be considered a risk factor for CVDs and efforts were made to retain PAF or PAF-like lipids in circulation by specific inhibitors of PAF-AH. For instance, a multicenter phase III STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial of 16,000 patients was conducted with darapladib, a specific PAF-AH inhibitor, by one of the leading pharmaceutical company – GlaxoSmithKline. However, the drug failed to significantly reduce mortality due to myocardial infarction and stroke (Marathe et al. 2014), inviting questions whether elevated levels of PAF-AH is a risk factor or a risk marker of inflammation. Nonetheless, overwhelming observations from in vitro, in vivo, and PAF-AH deficient subjects indicate a protective role for PAF-AH and hence can serve as a potential risk marker than risk factor (Marathe et al. 2014). Another imprecision is concerning the role of lyso PC, the product of PAF-AH action on acyl/oxidized diacyl phospholipids. Although lyso PC is not an effective PAF-R ligand, it is believed to promote atherogenesis and hence considered proinflammatory. However, the ascribed proinflammatory status to lyso PC does not hold good for reasons that its normal plasma concentration (140–150 μM) is very much higher than its action range (10–50 μM). Secondly, the authenticity of experiments that utilized commercial preparations of lyso PC/ lyso PAF is questionable, since it is now clear that the inflammatory properties falsely ascribed to lyso PC was due to the presence of trace amounts of PAF and PAF mimetics (Marathe et al. 2014). Thus, the ambiguity is not pertaining to the products of PAF-AH action but the nature of substrates for PAF-AH that can act as agonists/antagonists for the PAF-R.


PAF-AHs are calcium-independent PLA2s, catalyzing the hydrolysis of the short sn-2 residue of the potent proinflammatory lipid, PAF to form the inactive lyso PAF and free acetate. These enzymes are actively present both intracellularly and in plasma and act on a wide range of substrates, which includes alkyl PAF, acyl PAF, PAF-mimetics, and phospholipids with oxidized sn-2 residues. Since PAF-AH cleaves the sn-2 position of PAF and PAF-mimetics, it abolishes the proinflammatory signal triggered by PAF and PAF-mimetics and hence is rightly termed as “signal terminator.” Correspondingly, the decreased levels of PAF-AH or its activity in plasma, mainly due to loss of function mutation, are observed to be associated with many inflammatory disorders such as CVDs, asthma, sepsis, and systemic lupus erythematosus. However there are countervailing opinions suggesting PAF-AH to be proatherogenic inviting insights into regulation of PAF-AH in inflammatory settings, especially in CVDs, and require additional studies to explicate the nature of products of PAF-AH activity. A better understanding of the PAF-signaling cascade with an appreciative emphasis on the role of PAF-AH in inflammatory conditions has to be revisited.


  1. Bhosle VK, Rivera JC, Zhou T, Omri S, Sanchez M, Hamel D, et al. Nuclear localization of platelet-activating factor receptor controls retinal neovascularisation. Cell Discov. 2016;2:16017Google Scholar
  2. Blank ML, Snyder F, Byers LW, Brooks B, Muirhead EE. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem Biophys Res Commun. 1979;90:1194–200.PubMedCrossRefGoogle Scholar
  3. Blank ML, Lee T-C, Fitzgerald V, Snyder F. A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet-activating lipid). J Biol Chem. 1981;256:175–8.PubMedPubMedCentralGoogle Scholar
  4. Chen J, Yang L, Foulks JM, Weyrich AS, Marathe GK, McIntyre TM. Intracellular PAF catabolism by PAF acetylhydrolase counteracts continual PAF synthesis. J Lipid Res. 2007;48:2365–76.PubMedCrossRefGoogle Scholar
  5. Chen R, Brady E, McIntyre TM. Human TMEM30a promotes uptake of antitumor and bioactive choline phospholipids into mammalian cells. J Immunol. 2011;186:3215–25Google Scholar
  6. Elstad MR, Stafforini DM, McIntyre TM, Prescott SM, Zimmerman GA. Platelet-activating factor acetylhydrolase increases during macrophage differentiation. A novel mechanism that regulates accumulation of platelet-activating factor. J Biol Chem. 1989;264:8467–70.PubMedGoogle Scholar
  7. Farr RS, Wardlow ML, Cox CP, Meng KE, Greene DE. Human serum acid-labile factor is an acylhydrolase that inactivates platelet-activating factor. Fed Proc. 1983;42:3120–2.PubMedGoogle Scholar
  8. Foulks JM, Weyrich AS, Zimmerman GA, McIntyre TM. A yeast PAF acetylhydrolase ortholog suppresses oxidative death. Free Radic Biol Med. 2009;45:434–42.CrossRefGoogle Scholar
  9. Graham RM, Stephens CJ, Silvester W, Leong LL, Sturm MJ, Taylor RR. Plasma degradation of platelet-activating factor in severely ill patients with clinical sepsis. Crit Care Med. 1994;22:204–12.PubMedCrossRefGoogle Scholar
  10. Greenberg ME, Li XM, Gugiu BG, Gu X, Qin J, Salomon RG, et al. The lipid whisker model of the structure of oxidized cell membranes. J Biol Chem. 2008;283:2385–96.Google Scholar
  11. Hanahan DJ. Platelet activating factor: a biologically active phosphoglyceride. Annu Rev Biochem. 1986;55:483–509.PubMedCrossRefGoogle Scholar
  12. Hattori M, Adachi H, Aoki J, Tsujimoto M, Arai H, Inoue K. Cloning and expression of a cDNA encoding the beta-subunit (30-kDa subunit) of bovine brain platelet-activating factor acetylhydrolase. J Biol Chem. 1995;270:31345–52.PubMedCrossRefGoogle Scholar
  13. Henderson Jr WR, Lu J, Poole KM, Dietsch GN, Chi EY. Recombinant human platelet-activating factor-acetylhydrolase inhibits airway inflammation and hyperreactivity in mouse asthma model. J Immunol. 2000;164:3360–7.PubMedCrossRefGoogle Scholar
  14. Henson PM. Release of vasoactive amines from rabbit platelets induced by sensitized mononuclear leukocytes and antigen. J Exp Med. 1970;131:287–306.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lee TC, Malone B, Wasserman SI, Fitzgerald V, Snyder F. Activities of enzymes that metabolize platelet-activating factor (1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine) in neutrophils and eosinophils from humans and the effect of a calcium ionophore. Biochem Biophys Res Commun. 1982;105:1303–8.PubMedCrossRefGoogle Scholar
  16. Marathe GK, Pandit C, Lakshmikanth CL, Chaithra VH, Jacob SP, D'Souza CJ. To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase. J Lipid Res. 2014;55:1847–54.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Marrache AM, Gobeil F Jr, Bernier SG, Stankova J, Rola-Pleszczynski M, Choufani S, et al. Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. J Immunol. 2002;169:6474–81.Google Scholar
  18. Matsuzawa A, Hattori K, Aoki J, Arai H, Inoue K. Protection against oxidative stress-induced cell death by intracellular platelet-activating factor-acetylhydrolase II. J Biol Chem. 1997;272:32315–20.PubMedCrossRefGoogle Scholar
  19. McIntyre TM, Prescott SM, Stafforini DM. The emerging roles of PAF acetylhydrolase. J Lipid Res. 2009;50(Suppl):S255–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Prescott SM, Zimmermann GA, Stafforini DM, McIntyre TM. Platelet Activationg Factor and related lipid mediators. Annu Rev Biochem. 2000;69:419–45.PubMedCrossRefGoogle Scholar
  21. Stafforini DM. Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther. 2009a;23:73–83.PubMedCrossRefGoogle Scholar
  22. Stafforini DM. Functional consequences of mutations and polymorphisms in the coding region of the PAF acetylhydrolase (PAF-AH) gene. Pharmaceuticals. 2009b;2:94–117.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Stafforini DM, Prescott SM, McIntyre TM. Human plasma platelet-activating factor acetylhydrolase: purification and properties. J Biol Chem. 1987;262:4223–30.PubMedGoogle Scholar
  24. Teixeira-da-Cunha MG, Gomes RN, Roehrs N, Bozza FA, Prescott SM, Stafforini D, et al. Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH) administration. PLoS One. 2013;8:e74567.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, et al. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 1995;374:549–53.PubMedCrossRefGoogle Scholar
  26. Zhou G, Marathe GK, Willard B, McIntyre TM. Intracellular erythrocyte platelet-activating factor acetylhydrolase I inactivates aspirin in blood. J Biol Chem. 2011;286:34820–9.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Gopal Kedihithlu Marathe
    • 1
  • Shancy Petsel Jacob
    • 1
  • Mosale Seetharam Sumanth
    • 1
  • Chikkamenahalli Lakshminarayana Lakshmikanth
    • 1
  • Kandahalli Venkataranganayaka Abhilash
    • 1
  • Vyala Hanumanthareddy Chaithra
    • 1
  1. 1.Department of Studies in BiochemistryUniversity of MysoreMysuruIndia