www.ksmf.org/arhimed   arhimed@ksmf.org   [5/10/2025 8:11:08 PM] http://www.ksmf.org/arhimed/poglej.asp?id=31 Izražanje celicnih adhezijskih molekul na endotelnih celicah ledvic in horioidnega pleteža pri bolnikih s sistemskim lupusom eritematozusom Avtor: Miha Arnol Mentor: akad. prof. dr. Dušan Ferluga Somentor: znanst. sod. dr. Alenka Vizjak, dipl. biol. in as. mag. Vesna Jurcic, dr. med Izhodišce. Celicne adhezijske molekule (CAM) so strukturno in funkcijsko razlicne molekule celicnih membran. Omogocajo povezave med celicami in povezave celice s sestavinami zunajcelicnega matriksa. Igrajo pomembno vlogo pri morfogenezi, ohranjanju strukture tkiv, hemostazi, celjenju, aterogenezi, zasevanju tumorjev ter pri vnetnem in imunskem odzivu. Sistemski lupus eritematozus (SLE) je sistemska avtoimunska bolezen, ki jo patohistološko temeljno oznacujeta odlaganje imunskih kompleksov in vnetni odziv v številnih tkivih in organih. Ledvicno telesce in horioidni pletež sta najpogostejši mesti odlaganja imunskih kompleksov. Medtem ko so vnetne spremembe v ledvicnih telescih pogostne, pisane, predstavljene z razlicnimi oblikami lupusnega glomerulonefritisa, v horioidnem pletežu praviloma ne najdemo vnetnih sprememb. Vzrok za omenjeno razliko bi lahko bilo razlicno lokalno izražanje CAM. Namen. Preverili bomo hipoteze, da: a) se izražanje CAM na endotelnih celicah (EC) ledvic bolnikov s SLE, v primerjavi z normalno ledvico, poveca, b) je izražanje CAM na EC horioidnega pleteža pri bolnikih s SLE drugacno od izražanja v ledvicah in se, v primerjavi z normalnim horioidnim pletežem, ne poveca, c) je intenzivnost izražanja CAM na EC ledvic in horioidnega pleteža bolnikov s SLE povezana z intenzivnostjo patohistoloških sprememb. Metode. Tkivne vzorce smo zbrali v arhivu Inštituta za patologijo Medicinske fakultete v Ljubljani. S tradicionalnimi svetlobno- in elektronskomikroskopskimi ter imunofluorescentnimi preiskavami so bili doloceni patohistološke oblike lupusnega glomerulonefritisa, intenzivnost vnetja in obilnost imunskih odlag v ledvicah ter obilnost imunskih odlag v horioidnem pletežu. CAM smo prikazali z imunohistokemicno metodo, pri kateri smo uporabili že tovarniško pripravljena protitelesa za prikaz ICAM-1 in VCAM-1 molekule ter selektina E. Rezultati. V ledvicah bolnikov s SLE se je izražanje ICAM-1 molekule, v primerjavi z normalnimi ledvicami, povecalo statisticno znacilno (p< 0.05) na EC glomerulnih kapilar, arterij in ven. Povecanje izražanja VCAM-1 molekule in selektina E je bilo statisticno znacilno na EC vseh žilnih odsekov. Na EC normalnega horioidnega pleteža je bilo, v primerjavi z normalnimi ledvicami, izražanje ICAM-1 molekule podobno, izražanje VCAM-1 molekule in selektina E pa bolj obsežno. V horioidnem pletežu bolnikov s SLE nismo opazili statisticno znacilno povecanega izražanja CAM, z izjemo povecanega izražanja VCAM-1 molekule na EC kapilar. V primerjavi z ledvicami bolnikov s SLE, je bilo izražanje CAM manj intenzivno in manj obsežno in podobno izražanju v normalnem horioidnem pletežu. Pri bolnikih s SLE je bila intenzivnost izražanja ICAM-1 molekule na EC glomerulnih kapilar povezana z aktivnostjo lupusnega glomerulonefritisa, intenzivnostjo vnetja in obilnostjo imunskih odlag v ledvicnih telescih. V primeru VCAM-1 molekule in selektina E je bila ta povezava manj ocitna. Obilnost imunskih odlag v horioidnem pletežu bolnikov s SLE ni bila povezana z intenzivnostjo izražanja CAM. Zakljucki. Rezultati vecinoma podpirajo naše hipoteze. Prvic, izražanje CAM na EC ledvic bolnikov s SLE je, v primerjavi z normalno ledvico, povecano, kar verjetno kaže na pomembno vlogo CAM pri prehodu vnetnic v izvenžilni prostor in nastanku vnetja. Drugic, izražanje CAM se na EC horioidnega pleteža bolnikov s SLE vecinoma ne poveca, je manj intenzivno in obsežno, kot na EC ledvic bolnikov s SLE. Manj intenzivno izražanje CAM na EC horioidnega pleteža je verjetno eden od vzrokov za odsotnost vnetja. Tretjic, intenzivnost izražanja CAM je v ledvicah bolnikov s SLE le delno povezana z intenzivnostjo bolezenskih sprememb. Intenzivnost izražanja CAM na EC horioidnega pleteža bolnikov s SLE ni povezana z obilnostjo imunskih odlag. «» [Abstract / English version] Expression of cell adhesion molecules on kidney and choroid plexus endothelial cells in patients with systemic lupus erythematosus Author: Miha Arnol Mentor: akad. prof. dr. Dušan Ferluga Co-mentor: znanst. sod. dr. Alenka Vizjak, dipl. biol. in as. mag. Vesna Jurcic, dr. med Background. Cellular adhesion molecules (CAM) are structurally and functionally diverse cell surface molecules. They mediate cell-cell adhesion and cell-extracellular matrix adhesion. They play an important role in morphogenesis, maintenance of tissue structure, hemostasis, wound healing, atherogenesis, tumor metastatic spread, inflammatory and immune response. Systemic lupus erythematosus (SLE) is a multisystem disease of autoimmune origin, characterized principally by deposition of immune complexes and inflammatory response in different tissues. The most frequent sites of immune complexes deposition are glomeruli and choroid plexus. The glomeruli frequently show inflammatory response which can take form of different patterns of lupus nephritis. In contrast, the inflammation is usually absent in choroid plexus. The reason for this difference could be different regional expression of CAM. Objective. We will investigate the following hypotheses: a) The expression of CAM on kidney endothelial cells (EC) in lupus patients is increased, when compared with normal kidney. b) The expression of CAM on EC of choroid plexus in lupus patients is different from expression in kidney and is, when compared with normal choroid plexus, not increased. c) The intensity of CAM expression on EC of kidney and choroid plexus in lupus patients is correlated with intensity of pathohistologic changes. Methods. Experiments were performed on kidney and choroid plexus samples collected from the archives of Institute of Pathology, Medical faculty, University of Ljubljana. The pathohistological pattern of lupus nephritis, the intensity of inflammation in kidneys and immune complexes in kidneys and choroid plexus were determined by traditional light microscopic, electron microscopic and imunofluorescent studies. EC expression of CAM was quantitated immunohistochemically with comercial anti-ICAM-1, anti-VCAM-1 and anti-E-selectin antibodies. Results. The expression of ICAM-1 in lupus patients kidneys was statistically significantly upregulated (p< 0.05) on EC of glomerular capillaries, arteries and veins. The upregulation of VCAM-1 and E-selectin expression was statistically significant on EC of all vascular segments. The expression of ICAM-1 on EC of normal choroid plexus was similar, when compared to normal kidney, but more intensive for VCAM-1 and E-selectin. With the exception of increased VCAM-1 expression on capillaries, the CAM expression in choroid plexus of lupus patients was not statistically significantly upregulated and was, in comparison with the kidney expression, less intensive and similar to the pattern seen in normal choroid plexus. The intensity of ICAM-1 expression on EC of glomerular capillaries was corellated with the activity of lupus nephritis, intensity of inflammation and immune complexes deposits in glomeruli; for VCAM-1 and E-selectin corellation was less then for ICAM-1. There was no corellation between intensity of immune complexes deposits in choroid plexus of lupus patients and intensity of CAM expression. Conclusions. The results mostly corroborate our hypotheses. First, CAM expression on kidney EC in lupus patients is upregulated when compared with normal kidney. This points to an important role of CAM in transmigration of inflammatory cells and inflammatory response. Second, CAM expression on EC of choroid plexus in lupus patients is mostly not upregulated and is less intensive then in lupus patients kidneys. Less intensive CAM expression on EC of choroid plexus is probably one of the reasons why there is no inflammation. Third, intensity of CAM expression in lupus patients kidneys is only partialy correlated with the intensity of pathological changes. Intensity of CAM expression in lupus patients choroid plexus is not correlated with the intensity of immune complexes deposits.