title: Serum activity of platelet-activating factor acetylhydrolase is a potential clinical marker for leptospirosis pulmonary hemorrhage.
abstract: Pulmonary hemorrhage has been recognized as a major, often lethal, manifestation of severe leptospirosis albeit the pathogenesis remains unclear. The Leptospira interrogans virulent serogroup Icterohaemorrhagiae serovar Lai encodes a protein (LA2144), which exhibited the platelet-activating factor acetylhydrolase (PAF-AH) activity in vitro similar to that of human serum with respect to its substrate affinity and specificity and thus designated L-PAF-AH. On the other hand, the primary amino acid sequence of L-PAF-AH is homologous to the alpha1-subunit of the bovine brain PAF-AH isoform I. The L-PAF-AH was proven to be an intracellular protein, which was encoded unanimously and expressed similarly in either pathogenic or saprophytic leptospires. Mongolian gerbil is an appropriate experimental model to study the PAF-AH level in serum with its basal activity level comparable to that of human while elevated directly associated with the course of pulmonary hemorrhage during severe leptospirosis. Mortality occurred around the peak of pulmonary hemorrhage, along with the transition of the PAF-AH activity level in serum, from the increasing phase to the final decreasing phase. Limited clinical data indicated that the serum activity of PAF-AH was likely to be elevated in the patients infected by L. interrogans serogroup Icterohaemorrhagiae, but not in those infected by other less severe serogroups. Although L-PAF-AH might be released into the micro-environment via cell lysis, its PAF-AH activity apparently contributed little to this elevation. Therefore, the change of PAF-AH in serum not only may be influential for pulmonary hemorrhage, but also seems suitable for disease monitoring to ensure prompt clinical treatment, which is critical for reducing the mortality of severe leptospirosis.
authors.affiliation: Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yang
authors.forename: Shengnian
authors.initials: S
authors.lastname: Wang
authors.forename: Hengan
authors.initials: H
authors.lastname: Wang
authors.forename: Xucheng
authors.initials: X
authors.lastname: Jiang
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Guo
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000818:Animals; D001426:Bacterial Proteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005849:Gerbillinae; D006470:Hemorrhage / Q000175:diagnosis*; D007919:Leptospira / Q000201:enzymology; D007922:Leptospirosis / Q000175:diagnosis / Q000473:pathology*; D008171:Lung Diseases / Q000382:microbiology / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase