Leukocytes prostaglandin production

Besides 12-LOX in platelets, the 5-LOX isoforms are constitutive in neutrophils. Evidences indicate that LOXs are involved in inflammation diseases and in atherosclerosis. 5-LOX is the enzyme that catalyzes the formation of leukotrienes with potential role for leukocytes and platelets interaction and inflammation. After platelet and leukocyte stimulation, products of both COX-1 and 5-LOX pathways increase. COX-1 activity derivatives increase the vascular permeability mediated by prostaglandins and produce platelet aggregation mediated by TXA2. The product of the lipoxygenase pathway, 5-oxo-6,8,1 1,14-eicosatetraenoic acid (5-Oxo-ETE), induces leukocyte chemotaxis and inflammation. 5-Oxo-ETE is formed by the oxidation of 5S-hydroxy-ETE (5-HETE) by 5-hydroxyeicosanoid dehydrogenase (5-HEDH), a microsomal enzyme found in leukocytes and platelets (42). 

Rosmarinic acid has been found to have anti-inflammatory activity (Sahu et al., 1999). Some anti-inflammatory activity may also be attributed to camosol, which was found to inhibit cyclooxygenase in rat peritoneal leukocytes (Laughton et al., 1991). Anti-ulcerogenic activity also was found in rats given 70% alcohol extracts of rosemary (Dias et al, 2000). The anti-ulcerogenic activity was not due to an inhibition of prostaglandin production, but was related to an increase in the content of mucosal non-protein sulfhydryl groups. 

Gold alters the morphology and functional capabilities of human macrophages—possibly its major mode of action. As a result, monocyte chemotactic factor-1, interleukin-8, interleukin-IB production, and vascular endothelial growth factor are all inhibited. Intramuscular gold compounds also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivate the first component of complement, and suppress the phagocytic activities of polymorphonuclear leukocytes. Auranofin also inhibits release of prostaglandin E2 and leukotriene B4. 

Another group of compounds that are chemically related to the prostaglandins are the leukotrienes. These compounds are also derived from arachidonic acid and are linear oxidation products found in leukocytes (white blood cells). Leukotrienes are distinguished by containing a conjugated triene double-bond arrangement. The conversion of arachidonic acid to leukotrienes is as shown in Fig. 13-19. 

MOA Inhibit prostaglandin synthesis by decreasing activity of cyclo-oxygenase Decreases the deposition of urate crystals in joints by decreasing leukocyte motility Decreases the motility of PMN leukocytes Competitive inhibition of uric acid reabsorption at the proximal tubule Inhibits xanthine oxidase, thus preventing uric acid production... 

Peterson LD, Jeffery NM, Thies F, Sanderson P. Newsholme EA. Calder PC. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandins E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 1998 33 171-180. 

Immunosuppressive agents, alone or in combination, are commonly used to alter the immune processes that are responsible for the glomerulonephritides. Corticosteroids, in addition to their immunosuppressive effecL also possess anti-inflammatory activities. They reduce the production and/or release of many substances that mediate the inflammatory process, such as prostaglandins, leukotrienes, platelet-activating factors, tumor necrosis factors (TNFs), and interleukin-1 (IL-1). Movement of leukocytes and macrophages to the site of inflammation is also inhibited. The immunosuppressive effects of corticosteroids are mediated through the inhibition of the release... 

In one study (Davis, 1986), subcutaneous injections of A. barbadensis inhibited mustard-induced rat paw edema compared to control (p < 0.01). The effectiveness increased with the use of RNA and vitamin C (p < 0.001). Another study (Vazquez et al., 1996) showed that intraperitoneally administered aloe vera extracts decreased carrageenan-induced rat paw edema and peritoneal neutrophil infiltration in response to carrageenan. It was also shown that aloe vera decreased prostaglandin E2 production. Mice receiving subcutaneous injections with colorized aloe vera gel containing anthraquinones at doses of 1, 10, and 100 mg/kg for 7 d had no reduction in their wound diameter (Davis et al., 1987). However, those receiving the same doses of decolorized (i.e., without anthraquinones) aloe vera had a decrease in wound diameter. Rats injected with colorized aloe vera for 12 d also had a decrease in wound diameter. These same authors also noted that polymorphonuclear leukocyte (PMN) infiltration and inflammation are decreased by both colorized and decolorized aloe vera. 

A9. Akama, H., Ichikawa, Y., Matsushita, Y., Shinozawa, T., and Homma, M. Mononuclear cells enhance prostaglandin E2 production of polymorphonuclear leukocytes via tumor necrosis factor alpha. Biochem. Biophys. Res. Common. 168, 857-862 (1990). 

It is of interest how the presently accepted concept of aspirin and aspirinlike compounds involvement with PGs came about. The last of the aspirin theories to arise proposed that aspirin interfered with leukocyte migration to the site of injury, thus inhibiting the inflammatory process. A prostaglandin phase of inflammation, where PGs arose in the exudate of experimentally induced edema after the appearance of histamine and bradykinin, was already known. These two events appeared to coincide in the inflammatory process. Thus, the time was ripe. In studying the mediators responsible for the anaphylactic response in sensitized guinea pig lungs, Piper and Vane (1969) isolated histamine, SRS-A, and a new substance they called rabbit aorta contracting substance (RCS), a very unstable material (1 to 2 min) whose release, and presumably production, was selectively inhibited by aspirin-... 

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