Neutrophil degranulation, inhibition

Britigan BE, Hassett DJ, Rosen GM, Hamill DR, Cohen MS. Neutrophil degranulation inhibits potential hydroxyl-radical formation. Relative impact of myeloperoxidase and lactoferrin release on hydroxyl-radical production by iron-supplemented neutrophils assessed by spin-trapping techniques. Biochem J 1989 264 447 55. 

Pfizer s tenidap (CP-66,248) (157), another enolic compound, was also more potent (500-fold) toward CO over 5-LO inhibition in human ISN (0.032 /iM and 18 /iM, respectively) [379-381]. Efficacy in rheumatoid arthritis clinical trials has been reported [380,382] in patients, serum levels of acute phase proteins and synovial fluid levels of IL-1 were reduced by tenidap, in contrast to the lack of this effect with NSAIDs. Besides CO/5-LO inhibition, a variety of in vitro activities have been reported, including a number of effects on monocyte functions and differentiation [379], inhibition of neutrophil degranulation [382], inhibition of the activation of neutrophil collagenase [383], inhibition of leukocyte-endothelial cell adhesion [384], and inhibition of LTB4-induced neutrophil chemotaxis [385]. Al-... 

NO reacts with PUFAs to yield their respective nitroalkene derivatives that can be detected in plasma. These nitroalkene derivatives of various EFAs induce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and have endogenous PPAR-y ligand activity... 

Quercetin and other flavonoids are effective inhibitors of 02 -production by cells. Quercetin is a potent inhibitor of human neutrophil degranulation and 02 -production, and also inhibits the phosphorylation of neutrophil proteins accompanying neutrophil activation by phorbol myristate acetate. Quercetin can also suppress lipid peroxidation in several biological systems, such as mitochondria, microsomes, chloro-plasts, and erythrocytes. Silymarin, a 3-OH flavone present in Silybum marianum (the European milk thistle), protects rat liver mitochondria and microsomes from lipid peroxide formation induced by Fe " "-ascorbate and NADPH-Fe -ADP systems. Soybean isoflavonoids have shown antioxidative potency... 

Blackburn, W.D. Heck, L.W. Wallace, R.W. The bioflavonoid quercetin inhibits neutrophil degranulation, superoxide production, and the phosphorylation of specific neutrophil proteins. Biochem. Biophys. Res. Commun. 1987, 144, 1229-1236. 

Overall, results from all these studies suggest that the long-term reduction in fat consumption improved both in vivo and ex vivo measures of immune functions. Increased response in these immune functions will generally indicate increased protection that may be of clinical significance. Only one study has compared the effects of lipid infusion on ex vivo measures of immune functions and the in vivo markers for diseases (van der Poll et al., 1995). In this study, intralipid infusion caused up to a 70% reduction in the in vitro secretion of IL-lp, IL-6, and TNF-ot however, it did not influence inflammatory responses to endotoxin (fever, leukocytosis, release of TNF and its receptor) and even potentiated plasma endotoxin responses (release of IL-6 and IL-8 and neutrophil degranulation). The authors concluded that hypertriglyceridemia does not inhibit the in vivo responses to endotoxin. 

Histamine inhibits neutrophil chemotaxis due to HR2 triggering, which is mimicked by impromidine (HR2 agonist), but not by betahistine (HRl agonist). In addition, histamine inhibits neutrophil activation, superoxide formation and degranulation via HR2 [40]. Downregulation of... 

Evidence of a reduction in the number of acid-soluble SH-groups by feverfew extract in neutrophils at concentrations similar to those inhibiting neutrophil behaviour has been described [45]. It was suggested that interference with SH-groups alters assembly of microtubules which are known to be involved in phagocytosis and degranulation of neutrophils. 

Caribbean coral Pseudopterogorgia elisabethae discovered by Fenical et al. [47], Pseudopterosin E, Fig. (3) is the one with the best pharmacological profile, combining low toxicity and potent antiinflammatory activity. In human neutrophils, pseudopterosin E inhibits degranulation and formation of Ieukotrienes [2], In 1991, phase I clinical trials were initiated with pseudopterosin E as a topical anti-inflammatory agent. Recently, novel anti-inflammatory natural products have been isolated from this Caribbean soft coral [48,49], Japanese researchers reported the isolation of a group of compounds designated helioporins A-E, which are related to the pseudopterosins [1],... 

Just as neutrophils respond to fMLP [91], macrophages and mast cells exposed to IgE and other stimuli show activation of PhL C, formation of IP3 and mobilization of Ca2+ [102]. This is followed by degranulation with release of lysosomal enzymes and histamine. These ligand-induced responses are blocked by PTX. Further, introduction of GTPVS into the cells causes degranulation that is blocked by neomycin, a substance that inhibits polyphosphoinositide hydrolysis by PhL C and interferes with the action of IP3 to mobilize Ca2+ [100]. The data point to the existence of a PTX-sensitive Gp (PTX-sensitive Gp). 

Coles B, Bloodsworth A, Clark SR, Lewis MJ, Cross AR, Freeman BA, O Donnell VB. Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils. Circ. Res. 2002 91 375-381. 

Cromoglicate inhibits mast-ceU degranulation and histamine release induced by phosphohpase A2, but does not interfere with the interaction of antigen and reaginic antibodies. Evidence is accumulating that it has an important stabilizing action on leukocytes, apart from mast cells, such as neutrophils, eosinophils, and monocytes, and that it also affects nerve reflexes in the lung (2). 

Tetracyclines have many effects on cells involved in inflammatory reactions, including inhibition of neutrophilic functions, such as migration, phagocytosis, degranulation, and the production of free oxygen radical (1). Most of these effects are supposed to be due to chelation of divalent ions and can be partly reversed by the addition of calcium ions or zinc ions. Their ability to inhibit synthesis... 

Artocarpols from the root barks of Artocarpus rigida have been identified as anti-inflammation agents. Artocarpol C (798) strikingly inhibited the release of y5-glucuronidase and histamine from mast cell degranulation in a concentration-dependent manner (ICso 10.9 and 13.2 //M, respectively). Artocarpol C (798) also showed inhibitory effect on the formyl-peptide-stimulated superoxide anion formation in neutrophils (ICso 26.0 //M) [350]. Artocarpol I (803) exhibited similar inhibition of superoxide anion formation in neutrophils (ICso 10.9 //M) [351]. 

Although research at the transcription level has dominated pharmacological research on STLs in the last fes years, it should not be forgotten that evidence from earlier studies has indicated involvement of many downstream effects in their anti-inflammatory activity. One of the most prominent effects in this respect is related to anti-secretive activity due to membrane-stabilization. It was shown by Hall and coworkers that STLs inhibit the activity and release of lysosomal enzymes [46] furthermore, some STLs were demonstrated to inhibit mast-cell degranulation [68, 69] and, as found more recently, the release of human neutrophil elastase [70]. 

Apazone is a tNSAID that has anti-inflammatory, analgesic, and antipyretic activity and is a potent uricosuric agent. It is available in Europe but not the U.S. Some of its function may arise from its ability to inhibit neutrophil migration, degranulation, and superoxide production. 

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