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Involvement of autocrine and paracrine factors secreted from keratinocytes in the wound healing effects of malotilate?
JSID Abstracts/J.
EM
Dermatol. Sci. 8 (1994) 54-88
175
178
PHOSPHOLIPIDS (PL) IN THE ARTHUS REACTION SITES INDUCED IN GUINEA-PIG SKIN
STRUCTURAL BASIS OF HAIRLESS GUINEA FOR MODELS OF CUTANEOUS BIOLOGY
T. TACHfBANAl, S. TANlGUCHl2 and S. IMAMURA1. lDepartment of Dermatology, Faculty of Medicine, Kyoto University. Kyoto, and 2Department of Dermatology. Taigenkai Hospital, Bisai
H.SUEKI, CPOPP, K.KUDOH, G.F.MURPHY, and AMKLIGMAN, Depr.of DeonatoIogy, Showa Univ. Sch. of Med. Tokyo, Japan, and Dept. of Dermatology, Univ. of Pennsylvania Sch. of Med. , Pbiladelpbia, USA.
PIG
SKIN
We have already demonstrated that the impaired activity cf histamine-Nmethyltransferase (HMT). a major histamine-metabolizing enzyme. is a particular feature in the Arthus reaction sites and that HMT activity is regulated by such compounds in which a certain chemical structure is contained. We have also proposed that, among preformed mediators with such structure, only serotonin Increases in the reaction, which make an apparent mirror image with the decrease of HMT activity. In this study, we examined PL and related compounds in the Arthus reaction. Phosphatidylcholine (PC), P-ethanolamine, P-serine and P-inositol altered after the initiation of the reaction, whereas lysc-PC and lysoPAF. which reduce HMT activity in vitro. were not detected. Therefore, PL were considered not to inhibit HMT activity, but lo exhibit their proper effecls as newly-formed mediators.
176
179
IMloLVEMENT OF AtJCCRINE AND PARACRlNEFACTORSSECRElED FRW KERATINOCYTESIN THE WOUND HEALINGEFFECTSOF MALOTllATE? 0. oHGo A SAKAt.H.KOGA. Y. NIWANO and K. KANAI
INHIBITORYEFFECTS OF KETOTIFEN FUMARATE ON OPSONIZED ZYMOSAN-INDUCED CHPXILUNINESCENCE RESPONSESOF HUMAN NEUTROPHILS
Pharmacautbal Research Instlute. Nihon Nohyaku Co.. Ltd., 326-Z Oyamedacho. Kawachi-Nqano, Oaka, Jsqan We have found that msbtilate (diisopmpyl 1,3~lhiol-Zylaenemabnate) has a rtbwlative acttvtty on the pmliferatbn at human skin keratimcytns in vitro in relation la ttr wound healing effect% tn thk study. la iuflher determine tt aubcrlns and/or paramine Iadorn prcdwed by keratimcyter could be involved in the wound healing etfectsol mabtilrde. dac$s ot neutralttlng antibodies d these factors on Ihe proliferation ol keratincqws, librobbsta and endathelial celk wora investigatedhy using a mndnbned medium oblakwd from keratinoqtes cutlures. Results am summeriwd as lollows; 1. The augmsntod baxpomticm d li-TdR into keratinccytescutlured in exogenous growth ta!xor lree medium (KM) by mabtilate was completely nwralized by the addhim cf anti-TGF- and -bFGF anl+adies. while anti-EGF, -P&F. -TGFR and IL-1 anribodies showed w eltects. 2. The incarpwafbn of H-TdR into lbmbbsts and endothslial calls was inasssed when cutturad in malotllatsheatad keratinoc@derived mndiined medium. The augmented Vl-TdR incotpxatbn was neutralizedby ths addnbn of anti-TGFn antibody. 3. Increased TGFasecntion from keratinocytesby mabtilats was amtirmsd by ELBA. These resutb suggest that Iho increased secretbn of sulocrins!paracrinefactors such asTGFe tmm keratiwxytes by mabtilatsmukl be involvedin ikswound healing ettects in terms ot accelerated pmttteralion of keratincqles. librcblasts and endothelial cells.
N. KITAMURA,M. MIYASATO,K. TAGIJCHI,S. TSUDA and Y. SASAI, Department of Dermatology, Kurume University School of Medicine, Kurume, Japan
177 EPJDERMAL LANGEIUIANS
The effects of ketotife” fumarate(KF) and clemastine fumarate (CF) on neutrophil chemiluminescence(CL) responses t” zymosa” particles coated with either IgG(IgGZ),CJ(‘.%Z),or both(IC3Z) were examined in vitro. Opsonized symosans caused detectable neutrophil 0: elaborations evaluated by a MCLA-CLsystem,vith the order of light emission being 1’3Z>IgGZ>C3Z,a”d Increased neutrophil !Caz+)i measured by a” Aequorin-CL system. Both KF and CF inhibited these opsonized zymosan-induced responses of neutrophil MCLA,CL.but not Aequorin-CL,in a dose-dependent fashion.with the characteristics that inhibitory effects of CF was usually greater than those of KF. Using a 07 generation system(hypoxanthine-xanthine oxidase),no interference of these drugs with measurement of 0, by MCLA-CLwas also noted. These results suggest that both drugs may suppress neutrophil oxidative potential for 02 generation by means of preventing levelsofasignalrransductionpathway fromPKCtoNADPHoxids.se.
180 CELLS IN YtTfLIGo
THE MECHANISM OF ORALAND GENITALAPHTRAEIN BEHCET'S DISEASE ANALYZED USING A HEMORRHEOLOGICALTECHNIQUE -RHEOLOGICALACTIVITY OF NEUTROPHILSTO PDGF IN CLOTTED BLOOD AND TO ACTIVATED COMPLENBNTSIIJINA S, and OTSUKA F. Department of Dermatology, Institute of Clinical Medicine, Universityof Tsukuba, Japan We have ever evaluated that neutrophilsof Behcet's disease are rheologicallyactivated and show higher response to extrinsicplatelet-derivedgrowth factor (PDGF). The rheologicalactivity of neutrophilsdenoted by us represents adhesiveness,aggregabilityand deformabilityof the cells. Objective:We evaluated the response of neutrophilsof the disease to intrinsicPDGF produced by platelet coagulation in serum and to complementsin zymosan-activatedplasma, using micropore filtrationmethod. Results: After a" incubationwith serum, the micropore filtrationtime of unstable Behcet's disease was siEni.ficantly higher than normal individuals(pcO.001). Conclusion:Highs= response of neutrophilsto PDGF was detected in Behcet's disease and my provide the possible relation with the mechanism of oral and genital ulcers.
EM
Dermatol. Sci. 8 (1994) 54-88
175
178
PHOSPHOLIPIDS (PL) IN THE ARTHUS REACTION SITES INDUCED IN GUINEA-PIG SKIN
STRUCTURAL BASIS OF HAIRLESS GUINEA FOR MODELS OF CUTANEOUS BIOLOGY
T. TACHfBANAl, S. TANlGUCHl2 and S. IMAMURA1. lDepartment of Dermatology, Faculty of Medicine, Kyoto University. Kyoto, and 2Department of Dermatology. Taigenkai Hospital, Bisai
H.SUEKI, CPOPP, K.KUDOH, G.F.MURPHY, and AMKLIGMAN, Depr.of DeonatoIogy, Showa Univ. Sch. of Med. Tokyo, Japan, and Dept. of Dermatology, Univ. of Pennsylvania Sch. of Med. , Pbiladelpbia, USA.
PIG
SKIN
We have already demonstrated that the impaired activity cf histamine-Nmethyltransferase (HMT). a major histamine-metabolizing enzyme. is a particular feature in the Arthus reaction sites and that HMT activity is regulated by such compounds in which a certain chemical structure is contained. We have also proposed that, among preformed mediators with such structure, only serotonin Increases in the reaction, which make an apparent mirror image with the decrease of HMT activity. In this study, we examined PL and related compounds in the Arthus reaction. Phosphatidylcholine (PC), P-ethanolamine, P-serine and P-inositol altered after the initiation of the reaction, whereas lysc-PC and lysoPAF. which reduce HMT activity in vitro. were not detected. Therefore, PL were considered not to inhibit HMT activity, but lo exhibit their proper effecls as newly-formed mediators.
176
179
IMloLVEMENT OF AtJCCRINE AND PARACRlNEFACTORSSECRElED FRW KERATINOCYTESIN THE WOUND HEALINGEFFECTSOF MALOTllATE? 0. oHGo A SAKAt.H.KOGA. Y. NIWANO and K. KANAI
INHIBITORYEFFECTS OF KETOTIFEN FUMARATE ON OPSONIZED ZYMOSAN-INDUCED CHPXILUNINESCENCE RESPONSESOF HUMAN NEUTROPHILS
Pharmacautbal Research Instlute. Nihon Nohyaku Co.. Ltd., 326-Z Oyamedacho. Kawachi-Nqano, Oaka, Jsqan We have found that msbtilate (diisopmpyl 1,3~lhiol-Zylaenemabnate) has a rtbwlative acttvtty on the pmliferatbn at human skin keratimcytns in vitro in relation la ttr wound healing effect% tn thk study. la iuflher determine tt aubcrlns and/or paramine Iadorn prcdwed by keratimcyter could be involved in the wound healing etfectsol mabtilrde. dac$s ot neutralttlng antibodies d these factors on Ihe proliferation ol keratincqws, librobbsta and endathelial celk wora investigatedhy using a mndnbned medium oblakwd from keratinoqtes cutlures. Results am summeriwd as lollows; 1. The augmsntod baxpomticm d li-TdR into keratinccytescutlured in exogenous growth ta!xor lree medium (KM) by mabtilate was completely nwralized by the addhim cf anti-TGF- and -bFGF anl+adies. while anti-EGF, -P&F. -TGFR and IL-1 anribodies showed w eltects. 2. The incarpwafbn of H-TdR into lbmbbsts and endothslial calls was inasssed when cutturad in malotllatsheatad keratinoc@derived mndiined medium. The augmented Vl-TdR incotpxatbn was neutralizedby ths addnbn of anti-TGFn antibody. 3. Increased TGFasecntion from keratinocytesby mabtilats was amtirmsd by ELBA. These resutb suggest that Iho increased secretbn of sulocrins!paracrinefactors such asTGFe tmm keratiwxytes by mabtilatsmukl be involvedin ikswound healing ettects in terms ot accelerated pmttteralion of keratincqles. librcblasts and endothelial cells.
N. KITAMURA,M. MIYASATO,K. TAGIJCHI,S. TSUDA and Y. SASAI, Department of Dermatology, Kurume University School of Medicine, Kurume, Japan
177 EPJDERMAL LANGEIUIANS
The effects of ketotife” fumarate(KF) and clemastine fumarate (CF) on neutrophil chemiluminescence(CL) responses t” zymosa” particles coated with either IgG(IgGZ),CJ(‘.%Z),or both(IC3Z) were examined in vitro. Opsonized symosans caused detectable neutrophil 0: elaborations evaluated by a MCLA-CLsystem,vith the order of light emission being 1’3Z>IgGZ>C3Z,a”d Increased neutrophil !Caz+)i measured by a” Aequorin-CL system. Both KF and CF inhibited these opsonized zymosan-induced responses of neutrophil MCLA,CL.but not Aequorin-CL,in a dose-dependent fashion.with the characteristics that inhibitory effects of CF was usually greater than those of KF. Using a 07 generation system(hypoxanthine-xanthine oxidase),no interference of these drugs with measurement of 0, by MCLA-CLwas also noted. These results suggest that both drugs may suppress neutrophil oxidative potential for 02 generation by means of preventing levelsofasignalrransductionpathway fromPKCtoNADPHoxids.se.
180 CELLS IN YtTfLIGo
THE MECHANISM OF ORALAND GENITALAPHTRAEIN BEHCET'S DISEASE ANALYZED USING A HEMORRHEOLOGICALTECHNIQUE -RHEOLOGICALACTIVITY OF NEUTROPHILSTO PDGF IN CLOTTED BLOOD AND TO ACTIVATED COMPLENBNTSIIJINA S, and OTSUKA F. Department of Dermatology, Institute of Clinical Medicine, Universityof Tsukuba, Japan We have ever evaluated that neutrophilsof Behcet's disease are rheologicallyactivated and show higher response to extrinsicplatelet-derivedgrowth factor (PDGF). The rheologicalactivity of neutrophilsdenoted by us represents adhesiveness,aggregabilityand deformabilityof the cells. Objective:We evaluated the response of neutrophilsof the disease to intrinsicPDGF produced by platelet coagulation in serum and to complementsin zymosan-activatedplasma, using micropore filtrationmethod. Results: After a" incubationwith serum, the micropore filtrationtime of unstable Behcet's disease was siEni.ficantly higher than normal individuals(pcO.001). Conclusion:Highs= response of neutrophilsto PDGF was detected in Behcet's disease and my provide the possible relation with the mechanism of oral and genital ulcers.