Secretory Phospholipase A2 Enzymes in Acute Lung Injury

Abstract

The secretory phospholipase A 2 (sPLA 2 ) group of secreted enzymes hydrolyze phospholipids and lead to the production of multiple biologically active lipid mediators. sPLA 2 s and their products (e.g., eicosanoids) play a significant role in the pathophysiology of various inflammatory diseases, including life-threatening lung disorders such as acute lung injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS). The ALI/ARDS spectrum of severe inflammatory conditions is caused by direct (such as bacterial or viral pneumonia) or indirect insults (sepsis) that are associated with high morbidity and mortality. Several sPLA 2 isoforms are upregulated in patients with ARDS as well as in multiple ALI preclinical models, and individual sPLA 2 s exert unique roles in regulating ALI pathophysiology. This brief review will summarize the contributions of specific sPLA 2 isoforms as markers and mediators in ALI, supporting a potential therapeutic role for targeting them in ARDS.

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

“…Activated sPLA2-IIA is an inflammatory agent that is particularly destructive to cell biomembranes due to its ability to hydrolyzed fatty acids [ 73 – 75 ]. The membrane damage leads to the release of arachidonic acids and lysophospholipids; the arachidonic acids are then metabolized by cyclooxygenase to thromboxanes, prostacyclins, prostaglandins, etc.…”

Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus

“…Prior work by our group and others has also demonstrated that inhibition or genetic deletion of gVPLA 2 attenuates murine ALI induced by LPS or high tidal volume ventilation [28,29,32]. These prior studies provide a strong scientific premise for the important role of gVPLA 2 in ARDS [18]. The current study seeks to characterize the role of gVPLA 2 in mediating lung EC dysfunction and ALI induced by the clinical-relevant pathogen MRSA (USA300 strain).…”

“…Flow cytometry was used to sort the mPVEC through the selection of CD31+/CD45-cells [33]. mPVECs (passages [13][14][15][16][17][18][19] were grown in endothelial growth medium-2 (EGM-2) at 37 • C in a 5% CO 2 incubator.…”

“…The sPLA 2 enzymes produce multiple lipid mediators, such as leukotrienes that promote inflammation and modulate immune responses [12,13]. At least eleven different mammalian sPLA 2 enzymes have been identified to date, with several implicated in the pathogenesis of ALI/ARDS in both animal models and patients [14][15][16][17][18]. Of these, gVPLA 2 (or sPLA 2 -V) is a 14-kDa enzyme that mediates multiple biological effects including lipid metabolism, eicosanoid production, leukocyte migration, airway inflammation, transcriptional activity, phagocytosis, and thrombosis [13,[19][20][21][22].…”

Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

“…Investigations into the biological role of mammalian group IIA PLA 2 , also known as inflammatory PLA 2 , in the development of several pathologies of inflammatory and immunological origin have been described. Several studies have revealed that group IIA sPLA 2 s are present in high levels in rheumatoid arthritis [47][48][49][50], acute pancreatitis [51][52][53], septic shock [54,55], Crohn's disease and ulcerative colitis [56][57][58], respiratory distress syndrome [59][60][61], bronchial asthma and allergic rhinitis [59,62], atherosclerosis [63,64], autoimmune diseases [65], and cancer [66][67][68][69]. These observations imply that both local and systemic inflammation are associated with the release of sPLA 2 s in vivo, thus raising the unclear question of the role of these PLA 2 s in inflammatory reactions.…”