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. 2018 Aug;33(4):486-493.
doi: 10.1002/jca.21624. Epub 2018 Mar 23.

The Effects of galectin-3 Depletion Apheresis on Induced Skin Inflammation in a Porcine Model

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Free PMC article

The Effects of galectin-3 Depletion Apheresis on Induced Skin Inflammation in a Porcine Model

Nalu Navarro-Alvarez et al. J Clin Apher. .
Free PMC article

Abstract

Galectin-3 (Gal-3), a β-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.

Keywords: complete Freund's adjuvant; lesion induration; plasmapheresis; therapeutic-apheresis.

Figures

Figure 1
Figure 1
Schematic representation of the model. A. Schematic representation of the CFA inflammatory skin injection. B1-B8 indicate biopsy sites around CFA injection. Pigs were injected with CFA on the left (L) and right (R) side of the neck region behind the ears using 2 X 2-inch templates, separated by at least 2 inches along the dorsal line. CFA was injected into the center of each 1-inch square. B. Schematic representation Gal-3 depletion by plasmapheresis, with representation of Gal-3, its pentamers, and lattice structures in right box.
Figure 2
Figure 2
Gal-3 plasma levels in samples collected immediately pre- and post-column for experimental animal 23147 (p-value < 0.0001). A. Gal-3 levels (ng/mL) in plasma samples from a representative animal that were collected early (early) or at the end (late) of the apheresis procedure, pre- (Above) and post- (Below) Gal-3 depletion-apheresis column. * Below limit of detection. B. Comparison of Gal-3 levels (ng/mL) in porcine plasma with known concentrations (5 or 2.5 ng/mL), with or without dilution with post-apheresis plasma.
Figure 3
Figure 3
Comparison of area of induration surrounding each CFA injection site over time (Experimental n=2; Control n=3). A. The time course of skin induration following CFA injection treatment in experimental (red line) and control (blue line) animals. B. Individual experimental animals (23171 and 23147) compared with control animals (22877, 22681, 23166) at days 0.5 (12 hours), 3, and 37. Induration measurements are shown only for those animals with confirmed injection into the subcutaneous space based on skin depth measurements at autopsy.
Figure 4
Figure 4. Ex vivo
depletion of Gal-3 from human plasma (n=3). Gal-3 levels (ng/mL) in 3 individual samples, pre- (Above column), post-Gal-3 depletion column (Sepharose +M3/38 Ab) and post-control column (Sepharose-alone). The plasma samples were obtained from volunteers who signed informed consent forms to use their blood anonymously. * p-value < 0.05; *** p-value < 0.0001.

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