Tissue Distribution of the Lipocalin Alpha-1 Microglobulin in the Developing Human Fetus

Abstract

S U M M A R Y Alpha-1 microglobulin ( ␣ 1 m), a lipocalin, is an evolutionarily conserved immunomodulatory plasma protein. In all species studied, ␣ 1 m is synthesized by hepatocytes and catabolized in the renal proximal tubular cells. ␣ 1 m deficiency has not been reported in any species, suggesting that its absence is lethal and indicating an important physiological role for this protein To clarify its functional role, tissue distribution studies are crucial. Such studies in humans have been restricted largely to adult fresh/frozen tissue. Formalin-fixed, paraffin-embedded multi-organ block tissue from aborted fetuses (gestational age range 7-22 weeks) was immunohistochemically examined for ␣ 1 m reactivity. Moderate to strong reactivity was seen at all ages in hepatocytes, renal proximal tubule cells, and a subset of pancreatic islet cells. Muscle (cardiac, skeletal, or smooth), adrenal cortex, a scattered subset of intestinal mucosal cells, tips of small intestinal villi, and Leydig cells showed weaker and/or variable levels of reactivity. Connective tissue stained with variable location and intensity. The following cells/sites were consistently negative: thymus, spleen, hematopoietic cells, lung parenchyma, glomeruli, exocrine pancreas, epidermis, cartilage/bone, ovary, seminiferous tubules, epididymis, thyroid, and parathyroid. The results underscore the dominant role of liver and kidney in fetal ␣ 1 m metabolism and provide a framework for understanding the functional role of this immunoregulatory protein.

Redox properties of the lipocalin α1-microglobulin: Reduction of cytochrome c, hemoglobin, and free iron

“…In both these cases the iron should be in its reduced form. α 1 m is present in the intestinal epithelium, enriched at the tips of the microvilli [16,33] underscoring the former possibility. (3) The reducing activity of t-α 1 m may be part of a heme degradation mechanism.…”

“…This is caused by an array of small chromophore prosthetic groups attached to the amino acid residues C34, K92, K118 and K130, which are localized around the entrance of the lipocalin pocket [11,12]. α 1 m is found in blood and in connective tissue in most organs and is most abundant at interfaces between the cells of the body and the environment, such as in lungs, intestine, kidneys and placenta [13][14][15][16]. α 1 m has immunosuppressive properties, such as inhibition of antigeninduced proliferation of human peripheral lymphocytes, migration and chemotaxis of granulocytes [17,18], IL-2 production by T-cells [19], and activation of the mononuclear cells [20].…”

Heme Degradation and Vascular Injury

“…a 1 -Microglobulin, a member of the lipocalin family, is a 26-kDa plasma and tissue glycoprotein (2). a 1 -Microglobulin is an evolutionarily conserved immunomodulatory plasma protein (91). In all species studied, a 1 -microglobulin is synthesized by hepatocytes and catabolized in the renal proximal tubular cells (91).…”

“…a 1 -Microglobulin is an evolutionarily conserved immunomodulatory plasma protein (91). In all species studied, a 1 -microglobulin is synthesized by hepatocytes and catabolized in the renal proximal tubular cells (91). a 1 -Microglobulin is found in blood in free form and is tightly bound to IgA via a cystine-cystine bond (31).…”

NuMA Influences Higher Order Chromatin Organization in Human Mammary Epithelium

“…After removal of excess DAPI, samples were mounted with the ProLong antifade kit (Invitrogen). For HRP immunostaining of NuMA in breast tissue, 4-m paraffin sections of archival, normal resting or lactating breast tissues were processed using an avidin-biotinperoxidase method as described (Lö gdberg et al, 2000). Tissue samples were used according to Institutional Review Board approval 03-135E.…”