Lipopolysaccharide macrophages

Induced by bacterial lipopolysaccharides or immune cytokines in macrophages, smooth muscle cells, and glia cells. Ca2+ is not required for the enzyme activation. 

Inducible NO synthase (iNOS) is usually not constitutively expressed, but can be induced in macrophages by bacterial lipopolysaccharide (LPS), cytokines and other-agents. Although primarily identified in macrophages, expression of the enzyme can be stimulated in virtually any cell or tissue, provided the appropriate inducing agents have been identified (for review see [1] and [3]). 

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

Mai, U.E.H., Perez-Perez, G.I., Wahl, L.M., Wahl, S.M., Blaser, M.J. and Smith, P.D. (1991). Soluble surface proteins from HeUa acter pylori activate monocytes/macrophages by lipopolysaccharide-independent mechanism. J. Clin. Invest. 87, 894-900. 

Bai, S.K., Lee, S.J., Na, H.J. et al. 2005. Beta-carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation. Exp Mol Med. 37 323-334. 

Daemen, T., Veninga, A., Dijkstra, J., and Scherphof, G. (1989) Differential effects of liposomeincorpo-ration on liver macrophage activating potencies of rough lipopolysaccharide, lipid A, and muramyl dipeptide Differences in susceptibility to lysosomal enzymes. Immunol. 142, 2469-2474. 

Qureshi, N., Perera, P.-Y., Shen, J., Zhang, G., Lenschat, A., Splitter G., Morrison, D.C., and Vogel, S.N. (2003) The proteasome as a lipopolysaccharide-binding protein in macrophages Differential effects of proteasome inhibition on lipopolysaccharide-induced signaling events. J. Immunol. 171, 1515. 

Cho SY, Park SJ, Kwon MJ, Jeong TS, Bok SH, Choi WY, Jeong WI, Ryu SY, Do SH, Lee CS, Song JC and Jeong KS. 2003. Quercetin suppresses proinflammatory cytokines production through MAP kinases andNF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem 243(1-2) 153-160. 

LOX-dependent superoxide production was also registered under ex vivo conditions [55]. It has been shown that the intravenous administration of lipopolysaccharide to rats stimulated superoxide production by alveolar and peritoneal macrophages. O Donnell and Azzi [56] proposed that a relatively high rate of superoxide production by cultured human fibroblasts in the presence of NADH was relevant to 15-LOX-catalyzed oxidation of unsaturated acids and was independent of NADPH oxidase, prostaglandin H synthase, xanthine oxidase, and cytochrome P-450 activation or mitochondrial respiration. LOX might also be involved in the superoxide production by epidermal growth factor-stimulated pheochromo-cytoma cells [57]. 

Zhou, Q. et al., Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein, Infect. Immun., 73, 935, 2005. 

McCloskey, T.W., Todaro, J.A., and Laskin, D.L., Lipopolysaccharide treatment of rats alters antigen expression and oxidative metabolism in hepatic macrophages and endothelial cells, Hepatology, 16, 191, 1992. 

Chakravortty, D. et al., The inhibitory action of sodium arsenite on lipopolysaccharide-induced nitric oxide production in RAW 267.4 macrophage cells A role of Raf-1 in lipopolysaccharide signaling,./. Immunol., 166, 2011, 2001. 

Recently, the possibility to use C60 as anti-inflammatory compound has been reported (Huang et al., 2008). Fullerene-xanthine hybrids have been studied to determine if nitric oxide (NO) and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-activated macrophages can be inhibited by hybrid administration, finding positive results. The presence of xanthine moiety seems to be essential for the inhibition of LPS-induced TNF-a production, while the fullerene portion ameliorates the efficiency in LPS-induced NO production blockage, leading to a new promising class of potent anti-inflammatoiy agents. It is necessary to mention also the opposite results obtained by an amino acid fullerene derivative tested on human epidermal keratinocytes at concentration from 0.4 to 400 pg/mL. 

Liang-Takasaki CJ, Makela PH, Leive L (1982) Phagocytosis of bacteria by macrophages changing the carbohydrate of lipopolysaccharide alters interaction with complement and macrophages. J Immunol 128 1229-35. 

Chiou WF, Lin JJ, Chen CF. (1998) Andrographolide suppresses the expression of inducible nitric oxide synthase in macrophage and restores the vasoconstriction in rat aorta treated with lipopolysaccharide. Br J Pharmacol 125 327-334. 

To set up and validate the in vitro systems we initiated a study with rat Uver slices. Stimulation by Upopolysaccharide (LPS) in liver slices was used to evoke a pro-inflammatory response in the Uver. Lipopolysaccharide (LPS), a component of Gram-negative bacterial ceU walls (also called endotoxin), has been associated with tissue injury and sepsis. In the Uver LPS activates the resident macrophages, the Kupffer ceUs, which results in cytokine release [96]. Furthermore, LPS is cleared by the Uver, mainly by Kupffer ceUs [97]. One of the major features of endotoxic shock is the induction of nitric oxide S5mthase in the Uver [98]. Inducible nitric oxide synthase (iNOS), the expression of which is induced by LPS and cytokines, produces nitric oxide (NO) in large quantities [99]. 

A number of stimuli are known to act as inducers of TNF production (Table 5.10). Bacterial lipopolysaccharide represents the most important inducer, and TNF mediates the pathophysiological effects of this molecule. TNF biosynthesis is regulated by both transcriptional and post-transcriptional mechanisms. Macrophages appear to constitutively express TNF-a mRNA,... 

Gavish L, Perez LS, Reissman P, Gertz SD (2008) Irradiation with 780 nm diode laser attenuates inflammatory cytokines but upregulates nitric oxide in lipopolysaccharide-stimulated macrophages implications for the prevention of aneurysm progression. Lasers Surg Med 40(5) 371-378... 

---