Open AccessAntimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages
Author(s) -
Zughaier Susu M.,
Shafer William M.,
Stephens David S.
Publication year - 2005
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2005.00549.x
Subject(s) - respiratory burst , lipopolysaccharide , biology , tlr4 , nitric oxide , polymyxin b , zymosan , phagocytosis , microbiology and biotechnology , nadph oxidase , macrophage , cytokine , reactive oxygen species , innate immune system , immune system , biochemistry , immunology , antibiotics , endocrinology , in vitro
Summary Antimicrobial peptides (AMPs), in addition to their antibacterial properties, are also chemotactic and signalling molecules that connect the innate and adaptive immune responses. The role of AMP [α defensins, LL‐37, a cathepsin G‐derived peptide (CG117‐136), protegrins (PG‐1), polymyxin B (PMX) and LLP1] in modulating the respiratory burst response in human and murine macrophages in the presence of bacterial endotoxin [lipopolysaccharide (LPS) or lipooligosaccharide (LOS)] was investigated. AMP were found to neutralize endotoxin induction of nitric oxide and TNFα release in macrophages in a dose‐dependent manner. In contrast, macrophages primed overnight with AMP and LOS or LPS significantly enhanced reactive oxygen species (ROS) release compared with cells primed with endotoxin or AMP alone, while no responses were seen in unprimed cells. This enhanced ROS release by macrophages was seen in all cell lines including those obtained from C3H/HeJ (TLR4 – / – ) mice. Similar effects were also seen when AMP and endotoxin were added directly with zymosan to trigger phagocytosis and the respiratory burst in unprimed RAW 264.7 and C3H/HeJ macrophages. Amplification of ROS release was also demonstrated in a cell‐free system of xanthine and xanthine oxidase. Although AMP inhibited cytokine and nitric oxide induction by endotoxin in a TLR4‐dependent manner, AMP and endotoxin amplified ROS release in a TLR4‐independent manner possibly by exerting a prolonged catalytic effect on the ROS generating enzymes such as the NADPH‐oxidase complex.