Making Mountains out of Mole Hills: The Role of CD36 in Oxidized Phospholipid-driven Lung Injury
Year: 2023
Type: editorial
Abstract: Phospholipid-driven Lung InjuryPhospholipids are a core unit of cell biology, making up membranes, affecting membrane fluidity, facilitating membrane transport, participating in cellular signaling and cell-cell adhesion, storing energy, constituting a large component of lung surfactant, and influencing immune responses (1).However, in chronic inflammatory diseases including atherosclerosis and chronic obstructive pulmonary disease, oxidative stress is induced, which leads to the production of oxidized phospholipids (OxPLs).Mechanistically, oxidation of phospholipids occurs either enzymatically by lipoxygenases, which are upregulated during inflammation, or nonenzymatically in a lipid peroxidation reaction from reactive oxygen species or oxidizing pollutants such as ozone (2, 3).OxPLs activate inflammation primarily through recognition and internalization by scavenger receptors (SRs) or the activation of Toll-like receptors (TLRs) (4).Either SR or TLR recognition of OxPLs leads to the activation of NF-kB and the upregulation of proinflammatory cytokines such as IL-6, IL-1b, TNF-a, and adhesion molecules including intracellular adhesion molecule-1 (ICAM-1) and VCAM-1 (5).More recently, oxidatively fragmented phospholipids termed truncated OxPLs (Tr-OxPLs) have been identified and found to be increased in the circulation during oxidative stress (6).However, OxPLs have been more thoroughly characterized than Tr-OxPLs.Although OxPLs and Tr-OxPLs use similar mechanisms to activate inflammation, they differ in some areas.For example, Tr-OxPLs induce macrophages to upregulate an antioxidant response, whereas macrophages exhibit a more proinflammatory profile in response to full-length OxPLs (7).Therefore, it is important to study the mechanisms of Tr-OxPL-induced inflammation and injury in juxtaposition to full-length OxPLs.OxPLs are classically recognized by SRs, particularly CD36, which binds oxidized low-density lipoprotein (LDL), leading to the activation of macrophage inflammation, foam cell formation, and cytokine production (8).In addition, full-length OxPLs bind TLRs such as TLR2 and TLR4, which directly upregulate NF-kB and cytokine production (9).Although Tr-OxPLs are structurally similar, they differ enough from full-length OxPLs that they may induce inflammation through different mechanisms.In addition, it is not well characterized how Tr-OxPL contribute to chronic inflammatory diseases.It is therefore important to further study Tr-OxPLs and consider if Tr-OxPLs activate inflammation through SRs, TLRs, or both.Inhibiting CD36 is a prime candidate to block Tr-OxPL-induced inflammation because of its known role in binding OxPLs and oxidized LDL, leading to chronic inflammation and driving cardiopulmonary diseases.Synthetic amphipathic helical peptides have gained attention for targeting CD36.Originally designed as apoA-1 (apolipoprotein A-1) mimetic peptides to
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4387002118