Response of polymorphonuclear leukocytes to topical leukotriene B4 in healthy and psoriatic skin

Lammers, A.M.; Kerkhof, Peter C M van de

doi:10.1111/j.1365-2133.1987.tb05872.x

Cited by 25 publications

(9 citation statements)

References 5 publications

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“…Furthermore, repeated applications of LTB4 gave significantly lower amounts of intraepidermal neutrophils than a sin gle application [19]. These findings were confirm ed by Lammers and Van De Kerkhof [20] and suggest some sort of restraining mechanism for the extravasation of polymorphonuclear leukocytes (PMN) in psoriatic uninvolved skin in vivo. TGF-/3 has a restraining influence on the extravasation of peripheral white bloodcells [15].…”

Section: Discussionsupporting

confidence: 73%

Expression of endoglin in psoriatic involved and uninvolved skin

Rulo

Westphal

Kerkhof

et al. 1995

Journal of Dermatological Science

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Please be advised that this information was generated on 2018-05-11 and may be subject to change. JOURNAL OFD e r m a to lo g ic a AbstractEndoglin is a glycoprotein with TGF-jS binding capacity and is predominantly expressed on endothelial cells. In psoriasis, TGF-/3 has appeared to play a role in the extravasation of peripheral blood mononuclear cells via the endothelium. In order to find out more about the role of endoglin in psoriasis, immunohistochemical staining with PN-E2, a novel anti-endoglin, and of PAL-E, recognizing vascular endothelium, was carried out in psoriatic involved, psoriatic uninvolved and normal skin. The expression of the antigens was assessed semi-quantitatively using a fivepoint scale. In psoriatic involved skin, a high endoglin expression was found. In psoriatic uninvolved skin, however, we found that endoglin expression was significantly decreased compared with normal skin. The relevance of these findings to the pathogenesis of psoriasis is discussed.

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Section: Discussionsupporting

confidence: 73%

Expression of endoglin in psoriatic involved and uninvolved skin

Rulo

Westphal

Kerkhof

et al. 1995

Journal of Dermatological Science

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“…Some degree of tachyphy laxis to respond to mediators of inflammation might be of relevance in this respect. A reduced responsiveness of the clinically uninvolved psori atic skin to epicutaneous application of the eicosanoid leukotriene B4 has been demonstrated in previous experiments [37,38]. Such a defense sys tem against pro-inflammatory events could be interpreted as an attempt of the skin to keep psoriatic plaques restricted to sharply demarcated plaques.…”

Section: Mjp Cerritsen Et Al / Journal O F Dermatological Sciencementioning

confidence: 93%

Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin

Gerritsen

Elbers

Jong

et al. 1997

Journal of Dermatological Science

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The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16. 1997 Elsevier Science Ireland Ltd. All rights reserved

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“…is also reflected in an enhanced efficacy on the skin, two quantitative well-reproducible in vivo models for cutaneous inflammation were evaluated. The inflammatory response to epicutaneous application of LTB 4 has been evaluated extensively [8][9][10]. LTB 4 in ethanol at concentrations between 10 and 100 ng/10 Ìl induces accumulation of neutrophils, with a sharp maximum between 16 and 24 h. In this dose range a clear dose-response relationship has been shown.…”

Section: Discussionmentioning

confidence: 94%

Pharmacological Effects of a Specific Leukotriene B<sub>4</sub> Receptor Antagonist (VML 295) on Blood Leukocytes, Cutaneous Inflammation and Epidermal Proliferation

Seegers

Andriessen

Hooijdonk

et al. 2000

Skin Pharmacol Physiol

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VML 295 (LY 293111) is a potent and specific leukotriene₄ receptor antagonist. It has previously been shown in human volunteers that VML 295 at a dosage of 48 mg twice daily inhibits the ex vivo leukotriene B₄ (LTB₄)-induced upregulation of CD11b on peripheral blood neutrophils. A clear dose-response relatinship was shown. In addition, VML 295 inhibits various inflammatory aspects resulting from LTB₄ challenge of the skin, again showing a dose-response relationship. In view of the large variation in the elimination half-life of VML 295 (25–88.5 h) in individual human subjects, the present pharmacological study was designed to provide information on the pharmacodynamics of the drug by the assessment of VML 295 plasma concentrations, ex vivo LTB₄-induced CD11b upregulation of neutrophils, neutrophil accumulation in the skin following epicutaneous application of LTB₄ and epidermal regeneration following standardized surface trauma. A group of 36 healthy volunteers were treated in a double-blind study with VML 295 at 200 mg twice daily, VML 295 at 200 mg once daily or placebo for 7 days. Before treatment, at the end of treatment and following discontinuation of treatment, VML 295 plasma concentrations and CD11b upregulation of blood neutrophils were assessed. In 18 subjects, the effects of the three treatments on LTB₄-induced inflammatory were assessed before and at the end of treatment, and in the remaining 18 subjects the effects of these treatments on epidermal regeneration were assessed similarly. VML 295 at 200 mg either twice or once daily has a profound inhibitory effect on ex vivo LTB₄-induced CD11b upregulation of blood neutrophils, LTB₄-induced neutrophil accumulation in the skin, trauma-induced hyperproliferation of the epidermis and regenerative keratinization. The twice daily dose schedule was significantly more effective than the once daily regimen in reducing ex vivo CD11b stimulation of neutrophils, in blood samples collected 24 h after discontinuation of VML 295 treatment. The twice daily schedule tended to be more efficient in skin biopsies, although this difference was not statistically significant in the number of subjects investigated. A plasma concentration of 100 ng/ml proved to be the threshold for these effects. The profound biological effects, both systemically and cutaneously, as well as the safety profile, make VML 295 a promising drug for skin disorders characterized by epidermal proliferation and neutrophil accumulation.

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Response of polymorphonuclear leukocytes to topical leukotriene B4 in healthy and psoriatic skin

Cited by 25 publications

References 5 publications

Expression of endoglin in psoriatic involved and uninvolved skin

Expression of endoglin in psoriatic involved and uninvolved skin

Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin

Pharmacological Effects of a Specific Leukotriene B<sub>4</sub> Receptor Antagonist (VML 295) on Blood Leukocytes, Cutaneous Inflammation and Epidermal Proliferation

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