In vitro inhibition of human polymorphonuclear cell function by cloricromene

Bertocchi, Federico; Breviario, Ferruccio; Proserpio, Paolo; Wang, Ji Ming; Ghezzi, Pietro; Travagh, R. A.; Prosdocimi, Marco; Dejana, Elisabetta

doi:10.1007/bf00168664

Cited by 23 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Figure 3, a short preincubation of monocytes with chloricromene (1 min) was sufficient to reach maximal inhibition, suggesting that the drug is rapidly taken up by monocytes and then converted to its active metabolite, cloricromene acid, as previously described for platelets and polymorphonuclear leukocytes (Bertocchi et al, 1989). The acid metabolite cannot enter the cells when given as such and essentially is inactive in other biological tests performed (Squadrito et al, 1991).…”

Section: Effect Of Cloricromene On the Different Pathways Of Monocytesupporting

confidence: 55%

“…Cloricromene, besides reducing monocyte adhesion, is effective against monocyte chemotaxis (Bertocchi et al, 1989) and TNF release (Squadrito et al, 1992), by a mechanism of action which remains still obscure. This compound may induce a general inhibitory activity on platelets and polymorphonuclear leukocytes (Squadrito et al, 1991) possibly through its ability to modulate the levels of biochemical messengers which regulate cellular response.…”

Section: Effect Of Cloricromene On the Different Pathways Of Monocytementioning

confidence: 99%

“…We tested the effect of cloricromene on monocyte adhesion, since this compound, which exerts antithrombotic and vasodilator activities in vivo (Aporti et al, 1978;Prosdocimi et al, 1985), reduce both monocyte chemotaxis (Bertocchi et al, 1989) and TNF release (Squadrito et al, 1992 (Breviario et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene

Tranchina

Bernasconi

Dejana

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

The ability of the coumarin derivative cloricromene (8‐monochloro‐3‐β‐diethylaminoethyl‐4‐methyl‐7‐ethoxy‐carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. Cloricromene (10–200 μm) inhibited, in a concentration‐dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 μm. The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte adhesion to paraformaldehyde‐treated HUVEC. Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug. Both basal and chemoattractant‐mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to β2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of β2 integrins on the monocyte surface. When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1β (IL‐1; 50 ng ml−1) or tumour necrosis factor‐α (TNF; 100 u ml−1), the inhibitory effect of cloricromene was considerably reduced. The results of this study show that cloricromene may regulate monocyte adhesion to HUVEC, an event relevant in vivo in the pathogenesis of inflammatory and atherosclerotic processes.

show abstract

Section: Effect Of Cloricromene On the Different Pathways Of Monocytesupporting

confidence: 55%

Section: Effect Of Cloricromene On the Different Pathways Of Monocytementioning

confidence: 99%

See 1 more Smart Citation

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene

Tranchina

Bernasconi

Dejana

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…2), suggesting inhibition of membrane NAD(P)H oxidase activity. Other coumarins have previously been reported to block O 2 Ϫ by the neutrophil NADPH oxidase (8,39). Furthermore, prolonged treatment with the coumarin warfarin has been recently shown to reduce subsequent risk of cancer (43).…”

Section: Discussionmentioning

confidence: 99%

An NAD(P)H oxidase regulates growth and transcription in melanoma cells

Brar

Kennedy

Sturrock

et al. 2002

American Journal of Physiology-Cell Physiology

151

107

View full text Add to dashboard Cite

nant melanoma cells spontaneously generate reactive oxygen species (ROS) that promote constitutive activation of the transcription factor nuclear factor-B (NF-B). Although antioxidants and inhibitors of NAD(P)H oxidases significantly reduce constitutive NF-B activation and suppress cell proliferation (11), the nature of the enzyme responsible for ROS production in melanoma cells has not been determined. To address this issue, we now have characterized the source of ROS production in melanoma cells. We report that ROS are generated by isolated, cytosol-free melanoma plasma membranes, with inhibition by NAD(P)H oxidase inhibitors. The p22 phox , gp91 phox , and p67 phox components of the human phagocyte NAD(P)H oxidase and the gp91 phox homolog NOX4 were demonstrated in melanomas by RT-PCR and sequencing, and protein product for both p22 phox and gp91 phox was detected in cell membranes by immunoassay. Normal human epidermal melanocytes expressed only p22 phox and NOX4. Melanoma proliferation was reduced by NAD(P)H oxidase inhibitors and by transfection of antisense but not sense oligonucleotides for p22 phox and NOX4. Also, the flavoprotein inhibitor diphenylene iodonium inhibited constitutive DNA binding of nuclear protein to the NF-B and cAMP-response element consensus oligonucleotides, without affecting DNA binding activity to activator protein-1 or OCT-1. This suggests that ROS generated in autocrine fashion by an NAD(P)H oxidase may play a role in signaling malignant melanoma growth. superoxide anion; diphenylene iodonium; p22 phox ; gp91 phox ; p67 phox ; NOX1; NOX4; nuclear factor-B; cAMP response element; dicumarol REACTIVE OXYGEN SPECIES (ROS) generated by an NAD(P)H oxidase have been recently recognized as important signaling molecules for proliferation of normal cells. The role of a signaling NAD(P)H oxidase has been most extensively explored in vascular smooth muscle cells, where both p22 phox and the unique gp91 phox homolog NOX1 have been shown to be important for function of an NAD(P)H oxidase activity that mediates angiotensin IIinduced superoxide (O 2 Ϫ ) formation and redox-sensitive signaling pathways (19,30). Similar but structurally distinct NAD(P)H oxidases also perform signaling functions in normal vascular endothelial cells (18, 25) and adventitial cells (38), and the gp91 phox homolog NOX4 has recently been described in renal tubular epithelium (17, 45), fetal tissue (12), placenta (12), and proliferating vascular smooth muscle (30).Like normal cells, human tumor cells also produce substantial amounts of ROS spontaneously (15,37,49), and evidence points to a role for these ROS in signaling neoplastic proliferation. Mitogenic signaling through both Ras (22) and Rac (26) is mediated by O 2 Ϫ , and transfection with mitogenic oxidase NOX1 transforms normal fibroblasts (48) and creates cell lines that are tumorigenic in athymic mice (2). The NOX1 homolog has been found expressed in the Caco human colon carcinoma cells (12,28,48) and HepG2 hepatoma cells (28), and gp91 phox expression has been...

show abstract

“…Cloricromene weakly stimulates prostacyclin production in human cultured endothelial cells and rat thoracic aortic rings (Dejana et al, 1982), reduces thromboxane B2 release from platelets and inhibits platelet aggregation induced by various agents (Galli et al, 1980;Prosdocimi et al, 1985;. In addition, cloricromene inhibits both polymorphonuclear adhesion to endothelial cells and superoxide generation (Bertocchi et al, 1989), and causes coronary dilatation in the dog (Aporti et al, 1978).…”

Section: Introductionmentioning

confidence: 99%

Dissociation of the anti‐ischaemic effects of cloricromene from its anti‐platelet activity

Lidbury

Cirillo

Vane

1993

British J Pharmacology

View full text Add to dashboard Cite

1 Cloricromene is a non-anticoagulant coumarin derivative with anti-platelet and anti-leukocyte properties, which has beneficial effects in various models of ischaemia and shock. 2 We have assessed the effects of cloricromene on (a) ex vivo platelet aggregation, and (b) infarct size using a model of myocardial ischaemia in the anaesthetized rabbit.3 Cloricromene (1-1000 tgkg' min'I for 15min) induced a dose-dependent inhibition of ex vivo platelet aggregation, causing only a minimal increase in heart rate and no change in mean arterial blood pressure. The inhibitory activity was considerably stronger when platelet aggregation was induced by collagen than by ADP. 4 Cloricromene inhibited ex vivo platelet aggregation in rabbits pretreated with indomethacin (5 mg kg-') and this inhibition persisted for 30-60 min.5 The model of myocardial ischaemia involved 1 h occlusion of the first antero-lateral branch of the left coronary artery followed by 2 h of reperfusion. Infusion of cloricromene (30 or 300 gg kg-' min-'), ibuprofen (80 iLg kg-' min') or vehicle began 15 min prior to occlusion, and continued throughout the experiment.6 While area at risk was similar for all groups studied, cloricromene (30 or 300 ftg kg' min-') or ibuprofen caused a reduction in infarct size, and decreased myeloperoxidase activity in the tissue of the infarcted myocardium.7 Cloricromene at 300 pg kg-' min-' also reduced the occlusion-induced elevation of the ST-segment of the rabbit electrocardiogram, and inhibited platelet aggregation ex vivo. Ibuprofen or cloricromene at 30 fg kg-' min'-had no effect on either the ST-elevation or platelet reactivity.8 Thus, cloricromene exhibits a cardioprotective activity via an inhibition of leukocyte infiltration, in the presence (300 tLg kg-l min-') or absence (30 ltg kg'-min-') of inhibition of platelet activity ex vivo.The anti-aggregatory activity of cloricromene acts via a mechanism that is either different from, or in addition to, inhibition of cyclo-oxygenase, and is of long duration.

show abstract

In vitro inhibition of human polymorphonuclear cell function by cloricromene

Cited by 23 publications

References 18 publications

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene

An NAD(P)H oxidase regulates growth and transcription in melanoma cells

Dissociation of the anti‐ischaemic effects of cloricromene from its anti‐platelet activity

Contact Info

Product

Resources

About