Interaction and cellular localization of the human host defense peptide LL-37 with lung epithelial cells.
Lau. Y Elaine YE; Rozek. Annett A; Scott. Monisha G MG; Goosney. Danika L DL; Davidson. Donald J DJ; Hancock. Robert E W RE
Key Findings
- LL‑37 is actively taken up by A549 lung epithelial cells
- After entry, LL‑37 accumulates in the perinuclear region
- Uptake requires endocytosis mechanisms and microtubule‑dependent trafficking
- A549 cells have two LL‑37 receptors with high‑ and low‑affinity binding
Practical Outcomes
- For biohackers, the data suggest LL‑37 can get inside cells and potentially influence gene activity, but the paper doesn’t provide dosing or safety guidance. It hints that systemic or topical LL‑37 could have intracellular effects, yet more research is needed before practical protocols can be designed.
Summary
The study shows that the human peptide LL‑37 can enter lung cells, move toward the cell’s center, and likely interacts with two different cell surface receptors. This internal uptake depends on normal cell‑eating processes and the cell’s internal transport system, not on actin filaments.
Abstract
LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue culture by using biotinylated LL-37 and confocal microscopy. It was demonstrated that LL-37 was actively taken up into A549 epithelial cells and eventually localized to the perinuclear region. Specific inhibitors were used to demonstrate that the uptake process was not mediated by actin but required elements normally involved in endocytosis and that trafficking to the perinuclear region was dependent on microtubules. By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. These results indicate the mode of interaction of LL-37 with epithelial cells and further our understanding of its role in modulating the innate immune response.
Study Information
pubmed
2005
10.1128/iai.73.1.583-591.2005