Secretory Phospholipase A2–Albumin–Membrane Interactions: A Proposed Mechanism of Internal Cell and Tissue Injury in Systemic Inflammation
- 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792, USA
Abstract
Systemic inflammation in sepsis causes internal cell and tissue injury through mechanisms that remain incompletely understood. Secretory phospholipase A2 (sPLA2-IIA; hereafter, sPLA2), a potent inflammatory mediator whose circulating levels rise dramatically during sepsis, hydrolyzes membrane phospholipids in injured and dying cells, thereby releasing fatty acids and lysophospholipids that further amplify inflammation. Serum albumin—particularly a specific membrane-binding fraction (SFA)—normally acts as a cytoprotective scavenger of these lipid products, thereby maintaining membrane phospholipid homeostasis in concert with sPLA2. This perspective synthesizes nearly two decades of work demonstrating that the sPLA2–albumin interaction is a critical, underappreciated determinant of internal cell and tissue injury during systemic inflammation. As sPLA2 activity rises during sepsis, fatty acids generated from injured membranes progressively saturate albumin’s binding sites, inducing structural misfolding that abolishes its cytoprotective capacity and paradoxically enhances further sPLA2-mediated membrane degradation. Serial serum samples from ICU patients with sepsis revealed a statistically significant positive correlation between sPLA2 activity and albumin membrane-binding-site saturation, modifiable by nutritional intervention. Age-related albumin misfolding and oxidative stress are identified as important amplifying factors. The sPLA2–albumin axis represents a promising target for biomarker development and therapeutic intervention in critically ill patients.
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BibTeX
@article{tsao2026secretory,
title = {{Secretory Phospholipase A2–Albumin–Membrane Interactions: A Proposed Mechanism of Internal Cell and Tissue Injury in Systemic Inflammation}},
author = {Francis H. C. Tsao and Keith C. Meyer},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101461},
url = {https://www.mdpi.com/2218-273X/16/10/1461},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Secretory Phospholipase A2–Albumin–Membrane Interactions: A Proposed Mechanism of Internal Cell and Tissue Injury in Systemic Inflammation
AU - Francis H. C. Tsao
AU - Keith C. Meyer
PY - 2026
DA - 2026/10/07
JO - Biomolecules
DO - 10.3390/biom16101461
UR - https://www.mdpi.com/2218-273X/16/10/1461
AB - Systemic inflammation in sepsis causes internal cell and tissue injury through mechanisms that remain incompletely understood. Secretory phospholipase A2 (sPLA2-IIA; hereafter, sPLA2), a potent inflammatory mediator whose circulating levels rise dramatically during sepsis, hydrolyzes membrane phospholipids in injured and dying cells, thereby releasing fatty acids and lysophospholipids that further amplify inflammation. Serum albumin—particularly a specific membrane-binding fraction (SFA)—normally acts as a cytoprotective scavenger of these lipid products, thereby maintaining membrane phospholipid homeostasis in concert with sPLA2. This perspective synthesizes nearly two decades of work demonstrating that the sPLA2–albumin interaction is a critical, underappreciated determinant of internal cell and tissue injury during systemic inflammation. As sPLA2 activity rises during sepsis, fatty acids generated from injured membranes progressively saturate albumin’s binding sites, inducing structural misfolding that abolishes its cytoprotective capacity and paradoxically enhances further sPLA2-mediated membrane degradation. Serial serum samples from ICU patients with sepsis revealed a statistically significant positive correlation between sPLA2 activity and albumin membrane-binding-site saturation, modifiable by nutritional intervention. Age-related albumin misfolding and oxidative stress are identified as important amplifying factors. The sPLA2–albumin axis represents a promising target for biomarker development and therapeutic intervention in critically ill patients.
SN - 2218-273X
ER -