Scavenger endothelial cells of vertebrates: a nonperipheral leukocyte system for high-capacity elimination of waste macromolecules

Abstract

Studies over the last two decades have shown that mammalian nonmacrophagic liver endothelial cells clear the blood from numerous physiological and foreign waste macromolecules, such as polysaccharides and proteins released during extracellular matrix turnover, intracellular macromolecules, modified serum proteins, and bacterial and fungal proteins [Smedsrød, B., Pertoft, H., Gustafson, S. & Laurent, T. C. (1990) Biochem. J. 266, 313-327]. These macromolecules are released daily in gram-amounts in a normal human body and are effectively taken up and degraded by the liver endothelial cells. Recent studies show that bony fishes harbor a similar system of specialized nonmacrophagic scavenger endothelial cells in either kidney [Smedsrød, B., Gjøen, T., Sveinbjørnsson, B. & Berg, T. (1993) J. Fish Biol. 42, 279-291] or heart [Sørensen, K. K., Melkko, J. & Smedsrød, B. (1998) J. Exp. Biol. 201, 1707-1718], but not in liver. Using specific and extremely effective endocytosis, these fish scavenger endothelial cells function as their mammalian counterpart to eliminate soluble waste macromolecules from the circulation. We show here that species from all seven vertebrate classes carry a population of nonmacrophagic scavenger endothelial cells that efficiently eliminate an array of circulating waste macromolecules. Thus representing an important part of the vertebrate innate immune system, these scavenger endothelial cells display the following distribution in the different vertebrate classes: Gills in Agnatha and Chondrichtyes; heart or kidney in Osteichtyes; and liver in Amphibia, Reptilia, Aves, and Mammalia.

Figure 1

Cellular distribution of fluorescein isothiocyanate (FITC)-labeled formaldehyde-treated serum albumin 24 h after injection. Arrows point to accumulation of fluorescence in hagfish (a, high endothelium of the radial artery of the gills); lamprey (b, cavernous body, which is a branch of the afferent artery of the gill); cod (c, endocardium); salmon (d, endothelial cells lining blood sinusoids in trunk kidney); and lizard and rat (e and f, sinusoidal liver endothelial cells). [Scale bars, 50 μm (a and b), 25 μm (c and d), and 10 μm (e and f).]

Figure 2

Uptake of FITC-labeled ligands in primary cultures of cod endocardium and rat sinusoidal liver endothelial cells. (a) Cultured cod endocardial endothelial cells after a 1-h incubation with FITC-labeled formaldehyde-treated BSA (100 μg/ml) at 12°C. (b) cultured rat liver sinusoidal endothelial cells after a 1-h incubation with FITC-labeled hagfish collagen alpha chains (100 μg/ml) at 37°C. (Arrows, accumulation of probe in vesicles; Scale bars, 10 μm.)