Isolation of Tissue Plasminogen Activator from Skin Lesions with Allergic Vasculitis

Toki, Naotika; Tsushima, Hirofumi; Yamasaki, Masahiro; Yamasaki, Reiko; Yamura, T

doi:10.1111/1523-1747.ep12497854

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…Miskin and Ben-Ishai (1981) found that UV light induced u-PA in fibroblasts from patients with xeroderma pigmentosum, Toki et al (1982) purified u-PA from skin lesions with allergic vasculitis, and Hashimoto et al (1983) found that binding of pemphigus auto-antibodies to human epidermal cells resulted in elevated levels of u-PA. Furthermore, the type of plasminogen activator reported to be associated with inflammatory diseases has been u-PA (Unkeless et al, 1974a;Dane et al, 1985). Therefore, the present finding of t-PA as the only detectable plasminogen activator in psoriatic scales is remarkable.…”

Section: Discussionmentioning

confidence: 99%

Plasminogen activator in psoriatic scales is of the tissue-type PA as identified by monoclonal antibodies

et al. 1985

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Extracts of scale from four patients with psoriasis all contained plasminogen activator. All plasminogen activator activity was of the tissue-type (t-PA) as judged from the following criteria: all enzyme activity was inhibited by a monoclonal antibody against human t-PA, while there was no measurable inhibition by a monoclonal antibody against human urokinase-type plasminogen activator (u-PA); as determined by zymography the extracts contained one type of plasminogen activator which had an electrophoretic mobility identical to that of purified t-PA; this plasminogen activator was removed by passage through a Sepharose column coupled with a monoclonal antibody against t-PA, but not by passage through a column coupled with a monoclonal antibody against u-PA. On a molar basis the detection limit for u-PA was 10% of that of t-PA present.

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Section: Discussionmentioning

confidence: 99%

Plasminogen activator in psoriatic scales is of the tissue-type PA as identified by monoclonal antibodies

et al. 1985

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“…Plasmin generated by uPA participates in the turnover of extracellular matrix proteins in physiological and pathophysiological tissue remodeling 1, 2 . Abnormal expression of uPA is responsible for tissue damage in several pathological conditions, including rheumatoid arthritis 3 , allergic vasculitis 4 , xeroderma pigmentosum 5 , atherosclerosis 6 , and in particular, is a key factor for the invasive capacity of malignant tumours 7 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator

Kromann-Hansen

Lange

Sørensen

et al. 2017

Sci Rep

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Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two β-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general.

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“…Disturbance of the eqUilibrium between fibrin deposition and its removal by the fibrinolytic system, for example because of an increase in inhibitors and/or activator deficit, can result in accumulation of fibrin in the derma, as seen in numerous dermatologic affections: bullous dermatoses of the pemphigoid group (RYAN 1976;PANCONESI et al 1982), lichen planus (CRAWFORD and OGSTON 1975;LOTTI and FABBRI 1984), Schamberg's purpura (LoTTI et al 1985 b), and cutaneous vasculitis (CUNLIFFE 1968;TOKI et al 1982;LOTTI et al 1985c). There is instead an increase in fibrinolytic activity with excessive removal of fibrin from the microvessels which causes increased permeability of the dermal vessels in other diseases, such as urticaria (RYAN 1976;LOTTI et al 1985c), Majocchi's purpura (LOTTI et al 1985b), porphyria cutanea tarda (CHIMENTI et al 1981), psoriasis (RYAN 1973(RYAN , 1980BRUNETTI and LOTTI 1983), pemphigus vulgaris (PANCONESI et al 1982;HASHIMOTO et al 1982HASHIMOTO et al , 1984, primary irritant dermatitis , and pruritus aquagenicus (LOTTI et al 1984a(LOTTI et al , 1986b.…”

Section: Physiopathology Of the Cutaneous Fibrinolytic Systemmentioning

confidence: 99%

Pharmacology of the Skin II

1989

Handbook of Experimental Pharmacology

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PrefaceThe recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued unresolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology.We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.It was because of this burgeoning interest in pharmacology of skin and its diseases, that this book came about. Indeed it is long overdue and was planned several years ago; we console ourselves with the thought that the delay may have served to help define certain principles which were then only just emerging.The book is divided into two volumes which are independent but complementary; the first being an account of the general pharmacology of skin, the second volume being more concerned with disease and drugs. The first volume is divided into two parts, the one dealing with the pharmacology of skin systems and their control and the other with autocoids in normal and inflamed skin. This second volume has three parts; the first part deals with the methods of measurement which are becoming of increasing importance both in studying the pharmacological effects of drugs and the clinical pharmacology of skin; the second deals with toxicology in its widest sense -including metabolism and percutaneous absorption; and the third is an account both of specific drugs and the drugs used for specific diseases.

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Isolation of Tissue Plasminogen Activator from Skin Lesions with Allergic Vasculitis

Cited by 15 publications

References 32 publications

Plasminogen activator in psoriatic scales is of the tissue-type PA as identified by monoclonal antibodies

Plasminogen activator in psoriatic scales is of the tissue-type PA as identified by monoclonal antibodies

Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator

Pharmacology of the Skin II

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