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Chapter 24: Lipids: Lipid Mediators of Inflammation

You are studying the effects of a previously uncharacterized drug upon oral administration to experimental animals. Your tests involve examination of the effects of this compound within the gut following inducement of colitis-like symptoms. You find that administration of the drug to these animals leads to a reduction in the severity of inflammation in the gut and enhances a return to normal GI activity. Your test compound is most likely inducing the synthesis of which of the following compound?

A. LTB4

B. LXA4

C. PCI2

D. PGE2

E. TXA2

Answer B: The lipoxin, LXA4, inhibits polymorphonuclear leukocyte (PMN) chemotaxis, PMN-mediated increases in vasopermeability, and PMN adhesion and migration through the endothelium resulting in an attenuation of pro-inflammatory responses in the gut. LXA4 also stimulates phagocytosis of apoptotic PMN by monocyte-derived macrophages, which represents the resolution phase of inflammatory events.

A defect in which of the following enzyme activities would impair the production of the lipoxins by the classic pathway (ie, nonaspirin triggered) in neutrophils?

A. COX-1

B. COX-2

C. 5-LOX

D. 12-LOX

E. 15-LOX

Answer C: In one of the classical pathways of lipoxin synthesis, the interactions between epithelial cells and neutrophils require the activities of both 15-LOX and 5-LOX. Within the epithelial cells, the PLA2-mediated release of arachidonic acid serves as a substrate for 15-LOX and generates 15S-H(p)ETE. This latter compound will then diffuse out of the epithelial cells and be taken up by neutrophils where the activity of 5-LOX will then convert it into 15S-epoxytetraene, which is the precursor for LXA4 synthesis.

The lipoxins are characterized as pro-resolving compounds because they promote the resolution of an inflammatory response. Which of the following activities is associated with this pro-resolution function?

A. activation of TNF-α secretion

B. inhibition of polymorphonuclear (PMN) cell apoptosis

C. inhibition of the action of TGF-β

D. reduction in neutrophil infiltration at the site of inflammation

E. stimulation of IL-8 release

Answer D: Lipoxins and epi-lipoxins inhibit neutrophils (PMN) chemotaxis, PMN-mediated increases in vasopermeability, and PMN adhesion and migration ...

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