Galectin‐1 from ovine placenta

Abstract

In the present study we report the amino-acid sequence, carbohydrate specificity and overall biochemical and physicochemical properties of galectin-1, a β-galactoside-binding lectin from ovine placenta. The complete amino-acid sequence, obtained by tryptic and chymotryptic digestion, revealed that this carbohydrate-binding protein shares all the absolutely preserved and critical residues found in other members of the mammalian galectin-1 subfamily. Moreover, conformational changes induced by protein interaction with its specific disaccharide were investigated by fourth-derivative spectral analysis, intrinsic tryptophan fluorescence measurements and circular dichroism. The first two methods indicated changes in the environment of aromatic residues, in agreement with the role of Trp in carbohydrate binding. The quenching of the fluorescence emission upon addition of lactose, allowed us to calculate the K d for its interaction with the galectin, which was 0.157Ϯ 0.02 mM. The far-ultraviolet CD spectra is consistent with the large extent of β-sheet structure described for other galectins. Addition of lactose produced no significant changes, suggesting that it causes no modifications in the secondary structure of the lectin. In addition, we explored its potential cell-growth inhibitory activity and implications in T-cell death. Finally, we also provide evidence showing that antagonic properties of galectins-1 and -3 are reciprocally neutralized in a natural mixture of both proteins, suggesting that they could play an important role in the regulation of cell proliferation and death, according to physiological requirements at particular developmental stages of the placenta, thus allowing successful pregnancy to occur.

Adaptive Immune Responses During Pregnancy

“…Gal-1 is known to define autoimmunity, 70 inflammatory neurodegeneration, 71 cardiac inflammation, 72 and tumor escape. 73 74 and recent data confirm that it is not only expressed by the placenta itself 75 but also in uterine NK cells, 76 tolerogenic DCs, 55 and recent data show its importance when expressed in uterine MCs. 58 Pregnancies of Gal-1-deficient mice were first described as normal as the number of born embryos was apparently unaffected by this mutation.…”

Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2

“…4 Its presence has been localized within the central and peripheral immune compartment in thymic epithelial cells, 5 activated T cells 6,7 and activated macrophages. 8,9 It has also been found in immune privileged sites of the body such as placenta, 10,11 cornea 12 and testis. 13 Recent observations suggest that Gal-1 could play an important role in generating and maintaining central and peripheral immune tolerance.…”

“Galectin‐1 Induces Central and Peripheral Cell Death:Implications in T‐Cell Physiopathology”

“…Galectin-1 is also present in sites of immune privilege, such as placenta (Hirabayashi and Kasai, 1988;Iglesias et al, 1998a), cornea (Ogden et al, 1998) and prostate (Allen et al, 1991;Hirabayashi and Kasai, 1993). The presence of this protein in these vulnerable sites might contribute to mantain a state of tolerance by inducing apoptosis of inflammatory and activated T cells that could provoke injury, autoimmune damage or infection.…”

“…Accordingly, galectin-1 could also be proposed as an alternative regulatory signal to regulate immune privilege. Expression of this protein in first term gestation placenta would prevent inflammatory T cells from harming the fetus (Iglesias et al, 1998a (1995) showed that the T lymphoblastoid cell line MOLT-4 that was unsensitive to FasL-induced apoptosis, was susceptible to galectin-1. In contrast, the T lymphoblastoid cell line CEM, which was sensitive to FasL was resistant to galectin-l-induced apoptosis.…”

“…While galectin-1 has been shown to trigger T cell apoptosis (Perillo et a1.,1995;Rabinovich et al, 1998;Iglesias et al, 1998a), galectin-3 has been shown to stimulate proliferation (Yang et al, 1996;Iglesias et al, 1998b;Inohara et al, 1998). Similarly to members of the Bcl-2 family, galectins-1 and -3 belong to an additional family of proteins with high sequence homologies but opposite effects on cell survival.…”