HEMOKINI I HEMOKINSKI RECEPTORI U PATOGENEZI MULTIPLE SKLEROZE
Sažetak
Migracija leukocita u tkivo centralnog nervnog sistema (CNS) je jedan od procesa koji karakteriše patogenezu multiple skleroze (MS), a stimulisana je od strane hemokina. Kao konstitutivno eksprimirani u CNS, hemokini CXCL12 i CX3CL1 i njihovi receptori posreduju u uspostavljanju i održavanju tkivne homeostaze, dok su inducibilne promene njihove ekspresije u CNS povezane sa patogenezom MS. Hemokin CCL2, sintetisan od strane aktiviranih glijalnih i endotelnih ćelija u nervnom tkivu zahvaćenom inflamacijom, stimuliše infiltraciju CCR2+ monocita u CNS. Glijalni hemokini regulišu regrutovanje funkcionalno različitih subpopulacija T-limfocita tokom inflamacije u CNS, s obzirom da aktivirane glijalne ćelije unutar plakova sintetišu ligande za receptore koje eksprimiraju proinflamatorni Th1 limfociti (CXCR3 i CCR5) i antiinflamatorni Th2 limfociti (CCR4 i CCR8). Hemokin CCL20, koga produkuju Th17 limfociti i epitel horoidnog pleksusa, indukuje CCR6-posredovanu migraciju limfocita u CNS, što može imati i patogenu i protektivnu ulogu u MS, budući da CCR6 eksprimiraju proinflamatorni Th17 kao i antiinflamatorni regulatorni TREG limfociti. Zreli B-limfociti eksprimiraju receptor za hemokin CXCL13 (CXCR5), te je nivo CXCL13 u likvoru indikativan za intratekalni humoralni imunski odgovor u CNS tokom patogeneze MS. Lekovi koji se primenjuju u terapiji MS mogu da ostvaruju imunomodulatorne efekte preko uticaja na ekspresiju/aktivnost hemokina i hemokinskih receptora. Među aktuelnim terapeuticima teško je izdvojiti pojedinačni koji trajno efikasno suprimira bolest. Jedan od razloga za to leži upravo u kompleksnosti mreže hemokina i hemokinskih receptora, u pogledu njihove brojnosti i višestrukih funkcija koje imaju.
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