Antimicrobial and Immunomodulatory Activity of PMAP-23 Derived Peptides

Title:Antimicrobial and Immunomodulatory Activity of PMAP-23 Derived Peptides

Volume: 24 Issue: 7

Author(s): Edwin J. A. Veldhuizen*, Maaike R. Scheenstra, Johanna L.M. Tjeerdsma-van Bokhoven, Maarten Coorens, Viktoria A.F. Schneider, Floris J. Bikker, Albert van Dijk and Henk P. Haagsman

Affiliation:

• Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.165, 3508TD, Utrecht,Netherlands

Keywords: Antimicrobial peptide, innate immunity, defence, immunomodulation, LPS, alternative to antibiotics.

Abstract: Introduction: The Porcine Myeloid Antibacterial Peptide (PMAP)-23 is a porcine host defence peptide with strong antibacterial activity against Gram-positive and Gram-negative bacteria, and fungi.

Objective: PMAP-23 and truncated/mutated derivatives were tested for antibacterial and immunomodulatory activities to determine core elements of the peptide required for functionality.

Methods: PMAP-23 and truncated and/or mutated derivatives were synthesized. Antibacterial activity against Gram positive and negative bacteria was determined using colony counting assays. Cytotoxicity was measured against red blood cells and epithelial cells. Peptide induced cytokine production of epithelial cells was determined by ELISA. LPS neutralization was measured using isothermal titration calorimetry and inhibition of LPS induced cytokine production by macrophages. The effect of peptides on phagocytosis was performed by measuring uptake of fluorescently labelled beads by porcine macrophages.

Results: Truncation of the peptide did not lead to a strong reduction in antibacterial activity, but interestingly, all C-terminal truncated forms were strongly inhibited by salt addition, unlike the full length peptide or the two N-terminally truncated peptides. None of the peptides were hemolytic or toxic in concentrations up to 40 μM. Full length PMAP-23 induced IL-8 production in porcine epithelial cells, however, this activity was lost in all truncated peptides. None of the peptides bound LPS and subsequently did not inhibit LPS-induced cytokine production of monocytes. Finally, all PMAP-23 derived peptides reduced the uptake of beads by freshly isolated monocytes.

Conclusion: PMAP-23 is mainly antibacterial with only limited immunomodulating capacity; the full length peptide is required for the full spectrum of activities.

Cite this article as:

Veldhuizen J. A. Edwin *, Scheenstra R. Maaike , Tjeerdsma-van Bokhoven L.M. Johanna, Coorens Maarten , Schneider A.F. Viktoria, Bikker J. Floris, van Dijk Albert and Haagsman P. Henk, Antimicrobial and Immunomodulatory Activity of PMAP-23 Derived Peptides, Protein & Peptide Letters 2017; 24 (7) . https://dx.doi.org/10.2174/0929866524666170428150925

DOI https://dx.doi.org/10.2174/0929866524666170428150925	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305