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The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.

Publisher Summary The chapter presents a study on purification and properties of leukotriene C 4 synthase from guinea pig lung microsomes. Leukotriene C 4 synthase is the enzyme that catalyzes the conjugation of leukotriene (LT) A 4 with reduced glutathione (GSH). This enzyme is a novel member of the family of glutathione S-transferases and is distinct from other cytosolic glutathione S -transferases, and from the microsomal glutathione S -transferase that utilizes 1-chloro-2,4-dinitrobenze as a substrate. It has been partially purified and characterized from rat basophilic leukemia (RBL-1) cell microsomes and from guinea pig lung microsome. The conjugation of LTA 4 and GSH to form LTC 4 is monitored by on-line monitoring at 280 nm and quantitated by integrated absorbance. The chapter discusses the assay method, properties and purification, including the preparation of guinea pig lung microsomes. In the procedure for preparation of guinea pig lung microsomes glycerol is added to microsomes to achieve a concentration of 20% (w/v). To solubilize the enzyme, Triton X-102 and deoxycholate are added dropwise to concentrations of 0.4% each and then stirred for 1 hour at 4 degree.

Publisher Summary The chapter presents a study on cytochrome P-450LTB and inactivation of leukotriene B4 (LB4). The biological functions of chemotaxis and receptor binding of LTB4 are inactivated by progressive oxidation of C: 20. The ω-oxidation of this pathway is initiated by the enzymatic action of P-450LTB, a cytochrome P-450 mixed-function oxidase located, apparently exclusively, in human polymorphonuclear leukocytes (PMN). Cytochrome P-450LTB is distinct from the ω-hydroxylases, which ω-oxidize prostaglandins and lauric acid by both its substrate specificity and lack of immunological crossreactivity with polyclonal antibody to both these enzymes. Cytochrome P-450LTB shows a highly restricted substrate specificity, requiring the "correct" chirality of both the 5- and 12-hydroxyl group configuration and the cis and trans configuration of the double bonds and hydroxyl groups for maximal substrate activity. The chapter discusses cytochrome P-450LTB catalyzing the reactions. The second reaction, the apparent direct enzymatic oxidation of 20-OH-LTB4 by a cytochrome P-450, actually results from the enzymatic addition of a second hydroxyl group followed by the spontaneous dehydration of a dihydroxylated intermediate to an aldehyde. 20-CHO-LTB4 can also be hydroxylated to 20-COOH-LTB4 by cytochrome P-450LTB, but this reaction is relatively slow.