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 α1-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.

Decrease of Plasma Platelet-Activating Factor Acetylhydrolase Activity in Lipopolysaccharide Induced Mongolian Gerbil Sepsis Model

“…Previously, we found that Mongolian gerbil has its normal pPAF-AH level similar to that of human, and the patterns of the change of PAF-AH level in serum during the course of severe leptospirosis in gerbil model are similar to that of severe leptospirosis patients, including the levels of elevation [8]. These findings were consistent with the fact that LPS of Leptospira interrogans is much less virulent than that of Escherichia coli , and has little effect on the sepsis caused by leptospirosis [13].…”

Group A Streptococcus Secreted Esterase Hydrolyzes Platelet-Activating Factor to Impede Neutrophil Recruitment and Facilitate Innate Immune Evasion

“…The PAF acetylhydrolase activity of SsE appears at least to be as potent as the human plasma PAF acetylhydrolase. PAF acetylhydrolase activity has also been detected in bacteria and yeast [36], [37], [38]. While the yeast PAF acetylhydrolase enhances the viability of yeast under oxidative stress, the function of L. interrogans PAF acetylhydrolase and Est13 is not known.…”

Characterization of Streptococcal Platelet-Activating Factor Acetylhydrolase Variants That Are Involved in Innate Immune Evasion

“…An intracellular yeast group VII PAF-AH enhances the viability of yeast under oxidative stress (29). The spirochete Leptospira interrogans produces a PAF-AH (30). An apparently intracellular esterase Est13 from an earthworm gut-associated microorganism inhibits PAF-induced platelet aggregation (31).…”