Background: The function of secretory phospholipase A2 (sPLA2) is site dependent. In tissue, sPLA2 regulates eicosanoid production; in circulation, sPLA2 primes neutrophils; and in the intestinal lumen, sPLA2 provides innate bactericidal immunity as a defensin-related protein. Since parenteral nutrition (PN) primes leukocytes while suppressing intraluminal mucosal immunity, the authors hypothesized that (1) PN would diminish luminal sPLA2 activity but increase activity in intestinal tissue and serum and (2) stress would accentuate these changes.
Methods: Mice received chow, a complex enteral diet (CED), intragastric PN (IG-PN), or PN in experiment 1 and chow, chow+stress, PN, or PN+stress in experiment 2.
Results: In experiment 1, luminal sPLA2 activity was greatest in chow and decreased in CED, IG-PN, and PN, with PN lower than CED and IG-PN. Compared to that after chow, serum sPLA2 activity dropped after CED, IG-PN, and PN. Serum sPLA2 was higher in portal than systemic serum. In experiment 2, PN lowered luminal sPLA2 activity vs chow. Stress lowered luminal sPLA2 activity in chow, without change in PN. Following stress, luminal immunoglobulin A increased in chow but not PN. Serum sPLA2 activity increased in PN.
Conclusions: PN attenuates sPLA2 activity in intestinal fluid, consistent with suppressed innate mucosal defense. Stress suppresses luminal fluid sPLA2 activity in chow but not the immunoglobulin A response; PN impairs both. Stress significantly elevates serum sPLA2 in PN-fed mice, consistent with known increased neutrophil priming with PN. PN reduces innate bactericidal immunity of the gut but upregulates serum proinflammatory products poststress.
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http://dx.doi.org/10.1177/0148607111414025 | DOI Listing |
J Lipid Res
January 2025
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, Austria; Field of Excellence BioHealth - University of Graz, Graz, Austria. Electronic address:
Phospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phospholipases A (PAF-AH (also called Lp-PLA) and sPLA) and multifunctional enzymes capable of removing sn-2 residues in native and oxidized PLs (LCAT, PRDX6).
View Article and Find Full Text PDFChem Sci
January 2025
LAQV/Requimte, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto Rua do Campo Alegre, s/n 4169-007 Porto Portugal
Snake venom-secreted phospholipases A (svPLAs) are critical, highly toxic enzymes present in almost all snake venoms. Upon snakebite envenomation, svPLAs hydrolyze cell membrane phospholipids and induce pathological effects such as paralysis, myonecrosis, inflammation, or pain. Despite its central importance in envenomation, the chemical mechanism of svPLAs is poorly understood, with detrimental consequences for the design of small-molecule snakebite antidotes, which is highly undesirable given the gravity of the epidemiological data that ranks snakebite as the deadliest neglected tropical disease.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Lymphatic Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital; Clinical Center for Lymphatic Disorders, CMU, China. Electronic address:
This study offers new insights into the dual role of secretory phospholipase A2 (sPLA2) in lymphedema, highlighting its impact on lymphatic endothelial cell (LEC) functionality. Through transcriptomic analyses and co-culture experiments, we observed that sPLA2 has both protective and detrimental effects on human LECs (HLECs), mediated by macrophage activation. Our findings reveal that while low levels of sPLA2 promote LEC health, excessive sPLA2 leads to dysfunction, emphasizing the significance of the sPLA2/PLA2R axis and arachidonic acid metabolism (AA) in lymphedema pathology.
View Article and Find Full Text PDFToxicon
January 2025
Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Vital Brazil, 80, Cidade Universitária Zeferino Vaz, 13083-888, Campinas, SP, Brazil. Electronic address:
The venom of Colombian specimens of the rear-fanged snake Pseudoboa neuwiedii contains proteolytic and phospholipase A (PLA) activities, but is devoid of esterases. Mass spectrometric analysis of electrophoretic bands indicated that this venom contains C-type lectins (CTL), cysteine-rich secretory proteins (CRiSP), PLA, snake venom metalloproteinases (SVMP), and snake venom matrix metalloproteinases (svMMP). In this investigation, we extended our characterization of P.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address:
Secreted phospholipase A2s (sPLA2s) participate in physiological function by their enzyme and receptor binding activity. Muscle-type phospholipase A2 receptor (M-type PLA2R) is the sPLA2 binding protein with the highest affinity so far, and also inhibits the enzyme activity of sPLA2. There is species specificity and pH dependence for the binding of M-type PLA2R to sPLA2.
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