A cathelicidin family of human antibacterial peptide LL‐37 induces mast cell chemotaxis

TLDR

Mast cells are key effector cells in inflammation, widely distributed in tissues, and their local accumulation during inflammation requires directed migration. The authors hypothesized that the human cathelicidin-derived peptide LL‑37 acts as a mast cell chemotaxin. LL‑37 potently attracts mast cells in a dose‑dependent, bell‑shaped manner (optimal 5 µg/ml), acting chemotactically via Gi‑protein–phospholipase C signaling through high‑ and low‑affinity receptors, and may recruit mast cells to inflammatory sites.

Abstract

Summary The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. During inflammation, an increase in the number of mast cells in the local milieu occurs, and such accumulation requires directed migration of this cell population. As it has previously been reported that the human cathelicidin‐derived antibacterial peptide, LL‐37, stimulates the degranulation of mast cells, we hypothesized that LL‐37 could be a mast cell chemotaxin. The present study shows that LL‐37 is a potent chemotactic factor for mast cells. The chemotactic response was dose‐dependent and bell‐shaped, reaching an optimal concentration of 5 µg/ml. In addition, checkerboard analysis showed that cell migration towards this peptide was chemotactic rather than chemokinetic. Moreover, Scatchard analysis using 125 I‐labelled LL‐37‐derived peptide revealed that LL‐37 has at least two classes of receptors, namely high‐ and low‐affinity receptors, on mast cells. Furthermore, the competitive binding assay suggested that LL‐37 is unlikely to utilize formyl peptide receptor‐like 1 (FPRL1), a functional LL‐37 receptor for neutrophil and monocyte migration, on mast cells. In addition, the treatment of cells with pertussis toxin and phospholipase C inhibitor, U‐73122, inhibited LL‐37‐mediated migration, indicating that LL‐37 induces mast cell chemotaxis through a Gi protein‐phospholipase C signalling pathway. These results show that besides its antibacterial activities, LL‐37 may have the potential to recruit mast cells to inflammation foci.