Lactic acid suppresses MRGPRX2 mediated mast cell responses.
Syed. Meesum M; Kammala. Ananth K AK; Callahan. Brianna B; Oskeritzian. Carole A CA; Subramanian. Hariharan H
Key Findings
- Lactic acid suppresses both early calcium signaling and later cytokine release from mast cells via MRGPRX2/MrgprB2
- The suppression works in human LAD2 cells, human skin mast cells, and mouse peritoneal mast cells and is pH‑dependent
- In mouse models, lactic acid reduced systemic anaphylaxis to a known MRGPRX2 ligand and decreased skin inflammation in a rosacea model
Practical Outcomes
- While the findings suggest that environments rich in lactate may blunt mast‑cell driven inflammation (potentially useful for asthma or skin flare‑ups), there’s no clear dosage or supplement protocol yet. Biohackers might consider that intense exercise, which raises lactate, could have short‑term anti‑allergic effects, but they should be cautious about acid‑base balance and not assume direct supplementation will replicate the results.
Summary
The study shows that lactic acid, a natural by‑product of glucose metabolism, can calm down mast cells that cause allergic‑type reactions by blocking the MRGPRX2 pathway. This calming effect was seen in lab cells and in mice, and it lowered severe allergy reactions and skin inflammation. The effect depends on the acidity level, so it’s not a simple “take lactate” fix, but it hints that high‑lactate conditions (like after intense exercise) might reduce certain inflammation spikes.
Abstract
MAS related G-protein coupled receptor X2 (MRGPRX2) is a G-protein coupled receptor (GPCR) expressed in human mast cells that has been implicated to play an important role in causing pseudo-allergic reactions as well as exacerbating inflammation during asthma and other allergic diseases. Lactic acid, a byproduct of glucose metabolism, is abundantly present in inflamed tissues and has been shown to regulate functions of several immune cells. Because the endogenous ligands for MRGPRX2 (substance P and LL-37) are elevated during pathologic conditions, such as cancer and asthma, and given that lactic acid levels are also enhanced in these patients, we explored the role of lactic acid in regulating mast cells response via MRGPRX2 and MrgprB2, the mouse orthologue of the human receptor. We found that lactic acid suppressed both the early (Ca<sup>2+</sup> mobilization and degranulation) and late (chemokine/cytokine release) phases of mast cell activation; this data was confirmed in LAD2, human skin and mouse peritoneal mast cells. In LAD2 cells, the reduction in degranulation and chemokine/cytokine production mediated by lactic acid was dependent on pH. In agreement with our in vitro studies, lactic acid also reduced passive systemic anaphylaxis to compound 48/80 (a known MRGPRX2/MrgprB2 ligand) and skin inflammation in a mouse model of rosacea that is dependent on MrgprB2 expression on skin mast cells. Our data thus suggest that lactic acid may serve to inhibit mast cell-mediated inflammation during asthma and reduce immune response during cancer by affecting mast cell activation through MRGPRX2.
Study Information
pubmed
2021
2021-08-08T00:00:00.000Z
10.1016/j.cellimm.2021.104422
26