Macrophage triggering with cecropin A and melittin-derived peptides induces type II nitric oxide synthase expression.

Abstract

Triggering of RAW 264.7 cells with a cecropin A-melittin hybrid peptide (CA(1-8)M(1-18)) promoted a rapid rise in the intracellular calcium concentration that was followed, after a lag period of 6 h, by nitric oxide synthesis through the expression of the cytokine-inducible form of nitric oxide synthase (type II NOS or iNOS). The maximal effect was obtained at peptide concentrations in the 2 to 5-microM range. Simultaneous incubation with the peptide and LPS abrogated the nitric oxide synthesis elicited after LPS treatment of the cells. CA(1-8)M(1-18) induced a rapid activation of nuclear factor kappaB as evidenced by the presence of p50/p65 heterodimers of the nuclear factor kappaB/c-Rel family in the nuclei of activated cells. This peptide also activated the reporter activity of cells transfected with a plasmid harboring a 1-kb fragment corresponding to the 5'-flanking region of the murine iNOS gene. CA(1-8)M(1-18) promoted apoptotic cell death at concentrations below 1 to 2 microM, whereas higher concentrations altered the plasma membrane integrity. These results suggest the involvement of multiple intracellular signaling pathways in the mechanism by which this peptide elicits macrophage triggering.

Structure–activity relationships of antibacterial peptides

“…Peptide‐based antibiotics exhibit diverse mechanisms of action, which include disruption of membrane integrity or interference with cell wall biosynthesis, protein synthesis, DNA replication, RNA transcription, and fatty acid biosynthesis (Nguyen et al, 2011 ; Nolan & Walsh, 2009 ; Velasco et al, 1997 ; Wang, 2014 ).…”

The antimicrobial peptide MetchnikowinII enhances Ptfa antigen immune responses against avian <i>Pasteurella multocida</i> in chickens

“…Antimicrobial peptides (AMPs), as a part of the innate immune system, are ancient responses evolved to guard a wide range of microbes. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes and mast cells, participating in innate immunity, some mammalian macrophages can be regulated by antimicrobial peptides which can change gene expression [ 5 , 27 ]. On the other hand, antimicrobial peptides play an important role in both the innate and adaptive immunity [ 12 ].…”