Figure 4.

A – Scheme showing potential interaction(s) among invading microbes including SARS-CoV-2, host cell (target tissue/cell), immunocytes including macrophages and bioactive lipids including GLA/DGLA/AA/EPA/DHA, LXA4, PGE2, lipid peroxides (LP), activity of PLA2 COX-2 and LOX enzymes, CO, NO, H2S, and soluble epoxide hydrolase (sEH) and their relationship to the ability of microbes to infect the host cell and the response of the host cell to infection. B – Similarly, potential interaction between tumor host cell (refers to surrounding normal cells present in the microenvironment of tumor) and the role of COX-2, LOX enzymes and the formation of PGE2/LXA4 and their effect(s) on tumor cell. Legend to Figure 4: A – When a microbe (including SARS-CoV-2) invades a normal cell (host cell), it may increase the production of PGE2 using its own (or host cell) COX-2. The microbe using its LPS or by activating host cell LOX enzymes leads to the formation of LXA4 that negates the synthesis or action of PGE2. Microbial infection activates immunocytes leading to release of IL-6 and TNF-α that enhance the production of NO, CO, H2S and other ROS that can kill the microbes. Microbes can also activate PLA2 that induces the release from the cell membrane lipid pool of AA/EPA/DHA that are utilized for the formation of PGE2, LXA4 and lipid peroxides. Depending on the stage of the inflammation initially there will be activation of iPLA2 (inducible phospholipase A2) that induces the release of AA that is directed to form PGE2 and activation of M1 resulting in inflammation. Once PGE2 levels reach a peak it triggers the activation of soluble PLA2 (sPLA2) and cytosolic PLA2 (cPLA2) inducing the release of a second wave of AA and simultaneously activation of LOX leading to the formation of LXA4 and M2. This results in suppression of inflammation and restoration of homeostasis. BALS especially AA/EPA/DHA/LXA4 and lipid peroxides kill the microbes including SARS-CoA2. Lipid peroxides, LXA4 and AA/EPA/DHA may inhibit the activity of soluble epoxide hydrolase that leads to suppression of inflammation. Mesenchymal stem cells (MSCs) produce LXA4 to bring about their beneficial actions. B – A similar set of events occurs in the presence of a tumor cell. There is a crosstalk between normal cells surrounding the tumor cell and immunocytes. Tumor cells have high COX-2 activity that may lead to increased formation of PGE2 (COX-2 of tumor cells may act on normal cells or on exposure to tumor cells normal cells may enhance their COX-2 activity). On exposure to the tumor cell, PLA2 of normal cells/immunocytes is activated to induce the release of AA/EPA/DHA to produce PGE2 or LXA4. If the released AA/EPA/DHA are converted to form excess lipid peroxides and/or LXA4, then tumor cell growth is inhibited or it undergoes apoptosis. If the activity of COX-2 dominates then AA is converted to PGE2 that induces immunosuppression and enhances tumor cell growth. IL-6 and TNF-α released by immunocytes induce the release of ROS that can enhance the formation of lipid peroxides to induce apoptosis of tumor cells. But both IL-6 and TNF-α can induce deficiency of AA/EPA/DHA in the tumor cells and surrounding normal cells and immunocytes by inhibiting the activities of desaturases. See text for further details.