The expression of fetuin in the development and maturation of the hemopoietic and immune systems

Abstract

The distribution and expression of fetuin, a fetal plasma protein that has been shown to have a wide-spread intracellular presence in many developing tissues including the central nervous system, has been studied in the developing immune and hemopoietic organs of fetal and adult sheep. The presence of fetuin was demonstrated using immuno-cytochemistry and expression of fetuin was studied using northern blot analysis and in situ hybridization. In the developing sheep fetus, fetuin was shown to be expressed first in the hemopoietic cells of the fetal liver and subsequently in the forming spleen. The very first stromal, bone marrow-forming cells, also expressed fetuin mRNA. These cells became more numerous during gestation and by embryonic day (E)115 (term is 150 days), fetuin-expressing cells were identified morphologically to be monocytes/macrophages. Fetuin protein, on the other hand, was present in all hemopoietic and immune organs from the earliest age studied (E30) but was confined initially to matrix, mesenchymal tissue. Fetuin-positive cells could be identified in the spleen at E60 as early hemopoietic cells, in the lymph nodes at E60 as stromal cells and macrophages, and at E115 in the thymus as macrophages and squamous cells. In the adult, fetuin mRNA was only detectable by northern blot in the liver and the bone marrow. Using in situ hybridization in adult tissue, fetuin mRNA-positive cells were identified in the bone marrow to be monocytes/macrophages. Additionally, in the spleen germinal centres, fetuin mRNA was identified in cells with the morphology of dendritic cells. Using three separate cellular markers: lysozyme, S-100, and alpha 1-antitrypsin, the cellular identification of fetuin-positive cells was confirmed to be in the monocyte/macrophage lineage.

Fetuin‐A in the developing brain

“…Intrauterine fetuin-A colocalization with macrophages has already been reported in the literature. In contrast to adults, where fetuin-A-positive monocytes are restricted to the bone marrow, in fetal sheep fetuin-A is associated with monocytes resident in lymph nodes, thymus, spleen, and liver (Dziegielewska et al, 1996). Our findings demonstrate for the first time that activated brain microglia also shows fetuin-A immunoreactivity.…”

TGF-β receptor type II and fetuin in the developing sheep neocortex

“…In vivo, fetuin is widely present in the embryo and foetus (e.g., Reynolds et al 1983;Yang et al 1992;Saunders et al 1994;Dziegielewska et al 1996), but its expression is confined to the forming skeletal muscle, cartilage/bone tissue, bone marrow, liver and the central nervous system in the developing animal. In contrast, in the adult, fetuin is found only in the plasma, liver and bone marrow and its expression is at much lower levels than during development (Yang et al 1992;Saunders et al 1994;Dziegielewska et al 1996). A whole plethora of functions has been proposed for fetuin, but no definite role has been established (see Dziegielewska and Brown 1995 for review).…”

“…These were goat anti-rabbit gold conjugates (Auroprobe GAR one, Amersham, UK) diluted 1:50. The positive complex was visualised with silver enhancer (Boehringer Mannheim, Germany) as described previously (Dziegielewska et al 1996). Negative controls, included in each run, consisted of sections from which the primary antibody was omitted.…”

Proteomic analysis of amniotic and allantoic fluid from buffaloes during foetal development

“…AHSG functions in the regulation of calcium metabolism and participates in osteogenesis (Zheng, Liu, Wang, & Jin, 2013). It is also involved in embryonic development and placental transport (Briana et al, 2008;Dziegielewska et al, 1996); these functions may explain the presence of AHSG in the amniotic and allantoic fluids in our study.…”