Inhibition by manoalide of fmlp-stimulated elastase release from human neutrophils

Vries, Gerald W. De; Amdahl, Lawrence D.; Kramer, Kathryn; Wheeler, Larry A.

doi:10.1016/0006-2952(90)90090-8

Cited by 14 publications

(17 citation statements)

References 27 publications

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“…Figure 1 shows that the incubation of human PMNs in the presence of 30 nmol/l fMLP led to a linear increase in fluorescence after an initial lag period of approximately 10 s. This behavior is in line with the findings of De Vries et al [23] . The enzyme content in the cell lysate was measured and the amount of elastase released 60 min after the addition of 30 nmol/l of fMLP was 62.11 8 9.10% of the total cell enzyme content.…”

Section: Resultssupporting

confidence: 80%

“…It seems that full activation requires both internal and external calcium ions, but the effect of fMLP on calcium ion handling and capacitative calcium entry is complex and still unclear [49,50] . The release of elastase by PMNs in reply to fMLP is largely dependent on calcium mobilization [23,48] .…”

Section: Discussionmentioning

confidence: 99%

“…Elastase Release Assay PMN elastase release was measured spectrofluorometrically as described by Sklar et al [22] and De Vries et al [23] . The cells (5 !…”

Section: Collection Of Human Pmnsmentioning

confidence: 99%

“…Fluorescence was recorded using a Perkin-Elmer LS-5 fluorescence spec-132 trophotometer with excitation and emission wavelengths of respectively 380 and 460 nm. The enzyme rate was calculated using MCA (Sigma) as the standard, and was considered to be a reflection of the amount of elastase released from the cells [23] . The total elastase content of the PMNs was determined by means of cell lysis in 1% Triton X-100 (Sigma) as described by Sklar et al [22] , and enzyme release was quantified as the percentage of the amount of elastase released by stimulated neutrophils in comparison with the total enzyme content measured in the cell lysates.…”

Section: Collection Of Human Pmnsmentioning

confidence: 99%

“…A constant fluorescence signal was recorded with the excitation wavelength set at 340 nm, and the emission wavelength at 500 nm. The concentration of free cytosolic calcium was calculated according to Grynkiewicz et al [26] ] at resting level [23] . Maximal fluorescence was achieved by completely lysing the cells with 0.1% Triton-X and minimal fluorescence by complexing calcium with 10 mol/l EGTA [28] .…”

Section: Loading Fura-2 Into Pmns and Measuring Calcium Mobilizationmentioning

confidence: 99%

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Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase

et al. 2006

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Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin, and is considered a marker of inflammatory diseases. As the logical strategy to protect tissue is to inhibit excessive elastase activity, experimental and clinical researches have concentrated on trying to find efficient elastase inhibitors. As thymol, one of the major components of thyme oil with a phenolic structure, has been credited with a series of pharmacological properties, that include antimicrobial and antioxidant effects, the aim of this study was to explore whether it can also interfere with the release of elastase by human neutrophils stimulated with the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). After the neutrophils were incubated with increasing amounts of thymol (2.5, 5, 10, 20 µg/ml), elastase release was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that thymol inhibited fMLP-induced elastase release in a concentration-dependent manner, with the effects of 10 and 20 µg/ml being statistically significant. The behavior of cytosolic calcium mobilization revealed by fura-2 closely resembled that of elastase, thus suggesting that they may be related. The hydrophobic nature of thymol means that it can approach ion channel proteins through the lipid phase of the membrane, alter the local environment of calcium channels and thus inhibit capacitative calcium entry. In brief, thymol inactivates calcium channels machinery, thus triggering a corresponding reduction in elastase. The antibacterial and antimycotic activity of thymol is already well known, but our findings that it inhibits elastase extend our knowledge of the anti-inflammatory activity of this interesting molecule that is already credited with antioxidant activity. These two latter characteristics make thymol a molecule that can have helpful effects in controlling the inflammatory processes present in many infections.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

“…Elastase Release Assay PMN elastase release was measured spectrofluorometrically as described by Sklar et al [22] and De Vries et al [23] . The cells (5 !…”

Section: Collection Of Human Pmnsmentioning

confidence: 99%

Section: Collection Of Human Pmnsmentioning

confidence: 99%

Section: Loading Fura-2 Into Pmns and Measuring Calcium Mobilizationmentioning

confidence: 99%

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Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase

et al. 2006

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The antiinflammatory activity of topically applied novel calcium-channel antagonists

et al. 1995

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The antiinflammatory activities of two novel calcium-channel antagonists, AGN 190742 and AGN 190744, were evaluated in murine models of cutaneous inflammation. These 2(5H)-furanone ring compounds block both depolarization-dependent Ca2+ entry and receptor-mediated responses in GH3 cells. Topical application of AGN 190742 or AGN 190744 inhibits neutrophil infiltration and epidermal hyperplasia induced by repeated treatment of mouse skin with phorbol ester. AGN 190744 also is active in an arachidonic acid model of acute inflammation. These data suggest that topical application of calcium-channel antagonists can inhibit cutaneous inflammatory responses and that AGN 190742 and/or AGN 190744 may serve as useful pharmacological probes for examining these responses in vivo.

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Effects of scalaradial, a novel inhibitor of 14 kDa phospholipase A2, on human neutrophil function

Barnette

Rush

Marshall

et al. 1994

Biochemical Pharmacology

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Inhibition by manoalide of fmlp-stimulated elastase release from human neutrophils

Cited by 14 publications

References 27 publications

Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase

Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase

The antiinflammatory activity of topically applied novel calcium-channel antagonists

Effects of scalaradial, a novel inhibitor of 14 kDa phospholipase A2, on human neutrophil function

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