Lipopolysaccharide, polymorphonuclear

Mice that are homozygous for a disrupted Bx or B2 receptor gene are healthy, fertile and normotensive. In Bx-deficient mice, bacterial lipopolysaccharide-induced hypotension is diminished and the recruitment of polymorphonuclear leukocytes to the sites of tissue injury is impaired, and the animals show signs of hypoalgesia. Deletion of the B2 gene in mice leads to salt-sensitive hypertension and altered nociception. 

Lloyd AR, Biragyn A, Johnston JA, et al. Granulocyte-colony stimulating factor and lipopolysaccharide regulate the expression of interleukin 8 receptors on polymorphonuclear leukocytes. J Biol Chem 1995 270 28188-28192. 

Snyderman, R., Gewurz, H., Mergenhagen, S.E. (1968). Interactions of the complement system with endotoxic lipopolysaccharide Generation of a factor chemotactic for polymorphonuclear leukocytes. J. Exp. Med 128,259-75. 

Calvano, S.E., Thompson, W.A., Marra, M.N., Coyle, S.M., de Riesthal, H.F., Trousdale, R.K., Barie, P.S., Scott, R.W., Moldawer, L.L., Lowry, S.F. Changes in polymorphonuclear leukocyte surface and plasma bactericidal/permeability-increasing protein and plasma lipopolysaccharide binding protein during endotoxemia or sepsis. Arch Surg 129 (1994) 220-226. 

Wfe have recently carried out experiments with cell-based and animal models of inflammatory diseases. The experiments have revealed that human polymorphonuclear cells once activated with phorbol esters to cause an inflammatory response produce copious amounts of chlorinated polyphenol species. Rats treated with lipopolysaccharide (LPS) in an in vivo model of inflammatory disease heavily nitrate polyphenols in tissues (e.g., lung and liver) where inflammatory cell invasion occurs. These modified polyphenols are better antioxidants than their parent compound. Using a luciferase reporter gene assay in COS cells, both chloro- and nitrogenistein were shown to have 1-2 orders lower estrogen receptor activation than genistein itself. In summary, metabolism of polyphenols is rampant, but not always inactivating. 

Lloyd, A.R., Biragyn, A., Johnston, J.A., Taub, D.D., Xu, L.L., Michiel, D., Sprenger, H., Oppenheim, J.J., Kelvin, D.J., 1995. Granulocyte-colony stimulating factor and lipopolysaccharide regulate the expression of interleukin 8 receptors on polymorphonuclear leukocytes. J. Biol. Chem. 270, 28188-28192. 

Cassatella, M. A., Meda, L., Bonora, S., Ceska, M., and Constantin, G. (1993). Interleukin 10 inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 in mediating the production of IL-8 triggered by lipopolysaccharide./. Exp. Med. 110, 177-182. 

Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 1994 179 1695-1699. 

Wagner C, Deppisch R, Denefleh B, Hug F, Andrassy K, Hansch GM Expression patterns of the lipopolysaccharide receptor CD14, and the Fc receptors CD16 and CD64 on polymorphonuclear neutrophils (PMN) Data from patients with severe bacterial infection and LPS-exposed cells. Shock 2003 19 5-12. 

Marie C, Roman-Roman S, Rawadi G Involvement of mitogen activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentens membrane lipoproteins. Infect Immun 1999 67 688-693. 

Wright GG, Read PW, Mandell GL. Lipopolysaccharide releases a priming substance from platelets that augments the oxidative response of polymorphonuclear neutrophils to chemotactic peptide. J Infect Dis. 1988 157 690-696. 

Neutrophil apoptosis may be important in regulating the inflammatory process by controlling neutrophil numbers and thus activity. Exogenous inhaled nitric oxide is now a widely used therapy in patients with acute lung injury, and its effects on apoptosis may be important. In a model of nitric oxide-treated lung injury, Blaylock et al. (1998) incubated polymorphonuclear leucocytes isolated fi om venous blood for up to 16 h with and without 1.7 ng/ml lipopolysaccharide and the nitric oxide donor GEA-3162 or the peroxynitrite donor SIN-1. Apoptosis was attenuated when cells were exposed to lipopolysaccharide and both nitric oxide and peroxynitrite dose-dependently inhibited this suppression at all time points and was most apparent at 16 h (P = 0.004 and 0.001, respectively). 

Kupffer cells are major targets for lipopolysac-charides. Hepatic macrophages engulf lipopolysac-charide by phagocytosis (Mathison and Ul-EviTCH 1979). Lipopolysaccharide increased Oj " production in Kupffer cells (Bautista et al. 1990). Additionally, Upopolysaccharide induces migration of activated polymorphonuclear neutrophils into the Uver (Levy et al. 1967). Since these cells are the other source of free radicals, the intensity of polymorphonuclear neutrophil infiltration determines the degree of hepatic endotoxemia (Hewett et al. 1992). 

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