Galectin-1 in injured rat spinal cord: Implications for macrophage phagocytosis and neural repair

Abstract

Galectin (Gal)-1 is a small carbohydrate-binding protein and immune modulatory cytokine that is synthesized locally at the site of peripheral nerve injury. In this environment, Gal1 can promote regeneration of injured peripheral axons, in part by modifying the function of macrophages recruited to the site of injury. Unlike in injured peripheral nerves, macrophages do not promote axon regeneration in the injured central nervous system (CNS), perhaps because Gal1 levels are not regulated appropriately. Because the dynamics and cellular localization of endogenous Gal1 have not been rigorously characterized after CNS injury, we examined the spatio-temporal distribution of Gal1 in rat spinal cords subjected to a standardized contusion injury. Whereas Gal1 was not expressed in uninjured spinal cord, it was significantly upregulated after SCI, especially within the lesion core. Gal1 was expressed in ~40% of lesion-localized macrophages at 3–28 days post-injury (dpi), and in ~45% of astrocytes in the lesion border at 7–28 dpi. Most lesion-localized Gal1+ macrophages did not express the phagocytosis marker ED1, and Gal1+ cells contained less phagocytosed lipids. These data suggest time- and location-dependent regulation of Gal1 by macrophages (and astrocytes) could be important for modulating phagocytosis, inflammation/gliosis, and axon growth after SCI.

Galectin-1 expression imprints a neurovascular phenotype in proliferative retinopathies and delineates responses to anti-VEGF

“…In this regard, the role of Gal1 in neurodegeneration following brain injury has been largely appreciated. It has been reported that Gal1 is involved in the regulation of astrocyte reactivity [59] and that this lectin is important for modulating phagocytosis, inflammation, gliosis and axon growth after spinal cord injury [60, 61]. Moreover, astrocyte-derived Gal1 has been proposed to play a role in neuromodulation and microglia polarization in a model of multiple sclerosis [24] and in axonal degeneration in a model of amyotrophic lateral sclerosis [62].…”

High-throughput proteomics reveal alarmins as amplifiers of tissue pathology and inflammation after spinal cord injury

“…The small glycoproteins galectin-1 and −3 have broad functions in many tissues. In SCI their function is currently unclear; galectin-1 is thought to be neuroprotective 43 and to modulate macrophage behavior in the injury epicentre 44 , while galectin-3 is likely associated with secondary inflammatory events 45 .…”

Glial Cells Shape Pathology and Repair After Spinal Cord Injury

“…The immune response to injury in non-CNS tissue successfully sterilizes, remodels, and repairs the wound within weeks [7,153]. In contrast, inflammation begins soon after SCI, and a disproportionate pro-inflammatory response persists into chronic phases [154][155][156][157][158] without appreciably enhancing tissue repair or functional recovery. Given that microglia/macrophages display phenotypic plasticity in time based on local conditions [159], it appears that the chronic SCI environment promotes and maintains exaggerated proinflammatory microglia/macrophage polarization.…”