Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide.

Abstract

After in vitro exposure to lipopolysaccharide (LPS) or muramyl dipeptide (MDP), cultured resident mouse peritoneal macrophages were primed to display enhanced generation of superoxide anion (O2-) in response to stimulation by phorbol myristate acetate (PMA) or opsonized zymosan. Priming with LPS (1 microgram/ml) produced a sevenfold enhancement of PMA-stimulated O2- generation; priming was detected within 30 min and persisted for at least 4 d. Exposure to MDP (1 muM) primed the macrophages to double their O2- release; the response was first observed after 4 h and persisted for at least 3 d. The priming response was not observed with stereoisomers of MDP, which are inactive as adjuvants. LPS and MDP appeared to work directly on the macrophages rather than indirectly by interacting with adherent lymphocytes: (a) Addition of nonadherent cell populations that contained lymphocytes had no effect on the response. (b) The response was normal with cells from nude mice, which lack mature T lymphocytes. (c) Macrophages from C3H/HeJ mice, whose B lymphocytes fail to respond to LPS, were weak in their response to priming LPS; the addition of normal (C3Heb/FeJ) nonadherent cells had no effect on this weak response. (d) The macrophage-like cell line J774.1 also showed enhanced O2--generating capacity after a 4-h exposure to LPS or MDP. The O2--generating capacity of macrophages primed with LPS in vitro was equivalent to that previously observed with cells elicited in vivo by injection of LPS or activated by infection with Bacille Calmette-Guérin. The data suggest that previous exposure to bacterial products could prime macrophages to respond with increased production of toxic oxygen metabolites on contact with invading microorganisms or tumor cells.

Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response

“…Activated cells with increased metabolism therefore demonstrate enhanced oxygen radical production. When macrophages are activated, oxygen consumption increases markedly, resulting in the production of various ROS such as superoxides (24). Some of the ROS, produced during macrophage activation, serve as pathogen-killing agents, and some may affect the intracellular oxygen-redox balance.…”

Rap1 induces cytokine production in pro-inflammatory macrophages through NFκB signaling and is highly expressed in human atherosclerotic lesions

“…[25][26][27][28] Given the involvement of NFkB signaling in atherosclerosis, LPS was used to activate it and stimulate the production of NFkBdependent pro-inflammatory cytokines. 29,30 Indeed, LPS caused a sustained activation of p65 in THP-1 macrophages ( Fig.…”

Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat

“…Moreover, neutrophils are considered to be involved in the evolution of microvascular injury of the gut under acute pathological conditions (Hernandez et al, 1987;Kvietys et al, 1990;Chmaisse et al, 1994). During the development of such acute microvascular damage, neutrophils adhere to the vascular endothelium, releasing cytotoxic agents such as oxygen radicals and pro-inflammatory mediators including PAF (Sacks et al, 1978;Pabst & Johnston, 1980;Tauber & Babior, 1985;Hernandez et al, 1987;Kubes et al, 1990; . In addition to inhibiting neutrophil adhesion, NO donors can also inhibit the release of superoxide anions and PAF from neutrophils (Moilanen et al, 1993).…”