Identifying the Critical Domain of LL-37 Involved in Mediating Neutrophil Activation in the Presence of Influenza Virus: Functional and Structural Analysis.
Tripathi. Shweta S; Wang. Guangshun G; White. Mitchell M; Rynkiewicz. Michael M; Seaton. Barbara B; Hartshorn. Kevan K
Key Findings
- The central helical fragment GI‑20 reproduces LL‑37’s ability to increase neutrophil respiratory burst and NET formation when influenza virus is present.
- GI‑20 also lowers neutrophil IL‑8 production in response to the virus, matching the full peptide’s effect.
- Both GI‑20 and LL‑37 raise intracellular calcium and their activity is partially blocked by pertussis toxin, indicating dependence on FPR‑2 signaling.
- The N‑terminal fragment LL‑23 does not trigger these immune responses.
Practical Outcomes
- For DIY health enthusiasts, the work suggests that a smaller peptide (GI‑20) might be developed to modulate immune defenses without using the full LL‑37 molecule. However, the study provides no dosage, safety, or delivery information, so it isn’t ready for personal use. It mainly informs future peptide design rather than offering an immediate protocol.
Summary
The study shows that a short piece of the natural immune peptide LL-37, called GI-20, can still boost certain white‑blood‑cell actions against flu virus, just like the full‑length peptide. It works through a specific cell‑surface receptor (FPR‑2) and needs calcium inside the cells. A different short piece from the start of LL-37 (LL‑23) does not have these effects.
Abstract
The human cathelicidin LL-37 has been shown to play a role in host defense against influenza A viruses (IAV) through direct antiviral effects and through modulating inflammatory responses to infection. We recently showed that LL-37 increases neutrophil respiratory burst and neutrophil extracellular trap (NET) responses to IAV through engaging formyl peptide receptor 2 (FPR-2). In this paper we show that a fragment of LL-37, GI-20, which is composed of the central helical segment of the peptide, has similar effects as LL-37 on neutrophil activation. In addition to increasing respiratory burst and NET responses of the cells to IAV through an FPR-2 dependent mechanism, it reduces neutrophil IL-8 production to IAV (also like LL-37). The N-terminal fragment, LL-23, did not have similar effects. Both GI-20 and LL-37 increase neutrophil intracellular calcium levels and their ability to increase neutrophil activation responses was calcium dependent and partially inhibited by pertussis toxin. These studies show that the central helix of LL-37 retains the ability of LL-37 to modulate neutrophil responses through FPR-2. Based on our findings we developed a homology model of FPR-2 and performed docking experiments of LL-37 and GI-20 with the receptor.
Study Information
pubmed
2015
2015-08-26T00:00:00.000Z
10.1371/journal.pone.0133454
22
54