Tissue distribution of the lipocalin alpha-1 microglobulin in the developing human fetus

Alpha-1 microglobulin (alpha (1)m), a lipocalin, is an evolutionarily conse rved immunomodulatory plasma protein. in all species studied, arm is synthe sized by hepatocytes and catabolized in the renal proximal tubular cells. a lpha (1)m deficiency has not been reported in any species, suggesting that its absence is lethal and indicating an important physiological role for th is 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 immunohistochem ically examined for alpha (1)m reactivity. Moderate to strong reactivity wa s seen at all ages in hepatocytes, renal proximal tubule cells, and a subse t of pancreatic islet cells. Muscle (cardiac, skeletal, or smooth), adrenal cortex, a scattered subset of intestinal mucosal cells, tips of small inte stinal villi, and Leydig cells showed weaker and/or variable levels of reac tivity. Connective tissue stained with variable location and intensity. The following cells/sites were consistently negative: thymus, spleen, hematopo ietic cells, lung parenchyma, glomeruli, exocrine pancreas, epidermis, cart ilage/bone, ovary, seminiferous tubules, epididymis, thyroid, and parathyro id. The results underscore the dominant role of liver and kidney in fetal a lpha (1)m metabolism and provide a framework for understanding the function al role of this immunoregulatory protein.