The radioprotective efficacy of the rat acute-phase protein alpha2-macroglobulin on bone marrow cells

Abstract

The rat acute phase protein ?2-macroglobulin (?2M) plays an important role in the restoration of disrupted homeostasis by inhibiting different types of non-specific proteases and facilitating the transport of cytokines, growth factors and hormones. Previously, we observed that administration of ?2M to experimental animals prior to the infliction of life- threatening trauma in the form of scalding or total-body irradiation, significantly improved their survival rates. The aim of the present work was to evaluate the radioprotective effect on blood cells of ?2M that, when administered 30 min before irradiation with 6.7 Gy (LD50/30), provides 100% survival of experimental animals where in unprotected irradiated rats the said dose results in 50% lethality. We observed that rats pretreated with ?2M, after an initial decline, exhibited complete recovery of the leukocyte count due to the preservation of bone marrow cells, observed as a stable mitotic index. In untreated irradiated rats the decrease of the mitotic index reflected the significant destruction of bone marrow cells that resulted in a protracted decline in the leukocyte count. We conclude that the radioprotection provided by ?2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow.Pacovski alfa2-makroglobulin (?2M) ima vaznu ulogu u uspostavljanju narusene homeostaze inhibicijom razlicitih tipova nespecificnih proteaza i olaksavajuci transport citokina, hormona rasta i hormona. Nasa ranija istrazivanja su pokazala da administracija ?2M eksperimentalnim zivotinjama u traumama tipa opekotine ili ozracivanja celog organizma znacajno povecava njihovu stopu prezivljavanja. Cilj ove studije je bio izucavanje radioprotektivne uloge ?2M na celije kosne srzi. ?2M je apliciran 30 minuta pre ozracivanja pacova dozom od 6.7 Gy (LD50/30) X-zraka i omogucio je 100% prezivljavanje pacova za razliku od ozracenih pacova bez tretmana kod kojih je smrtnost bila 50%. Rezultati su pokazali da tretiranje zivotinja sa ?2M, nakon inicijalnog pada, omogucavaju potpuni oporavak broja leukocita kao posledica ocuvanja celija kosne srzi, sto se uocava preko stabilnog mitotskog indeksa. Kod ozracenih pacova bez tretmana signifikantno smanjenje mitotskog indeksa, kao posledica narusavanja celija kosne srzi, rezultuje i u prolongiranom padu broja leukocita. Na osnovu ovih rezultata moze se zakljuciti da se radioprotektivna uloga ?2M delom odvija putem citoprotekcije novih krvnih celija u kosnoj srzi.