TY - JOUR
T1 - Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence
AU - Pawlowic, Mattie C.
AU - Zhang, Kai
N1 - Funding Information:
We thank Drs. K.P. Chang (Rosalind Franklin University of Medicine and Science) and Jay Bangs (University of Wisconsin Madison) for providing us the rabbit anti- Leishmania GP63 antiserum and the rabbit anti- T. brucei BIP antiserum, respectively. This work was funded by US Public Health Service grants 1R15AI076909 (KZ) , 1R56AI081781 (KZ) and 5R03AI076662 (KZ) from the National Institute of Allergy and Infectious Diseases .
PY - 2012/11
Y1 - 2012/11
N2 - Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in Leishmania major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection.
AB - Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in Leishmania major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection.
KW - Leishmania
KW - Macrophage
KW - PAF-AH
KW - Phospholipase
KW - Platelet-activating factor
KW - Virulence
UR - http://www.scopus.com/inward/record.url?scp=84868446256&partnerID=8YFLogxK
U2 - 10.1016/j.molbiopara.2012.08.005
DO - 10.1016/j.molbiopara.2012.08.005
M3 - Article
C2 - 22954769
AN - SCOPUS:84868446256
VL - 186
SP - 11
EP - 20
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
SN - 0166-6851
IS - 1
ER -