Contributions
Abstract: EP1414
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Inflammation and tissue damage
Microglia constitute the population of resident tissue macrophages in the central nervous system (CNS) and are critically involved in the pathogenesis of Multiple Sclerosis (MS). Particularly, all MS brain lesions are associated with the presence of activated microglia but their activation mechanism remains elusive. Mainly, in response to a variety of stimuli, microglia up- or down-regulate surface molecule in order to undergo morphological transformation from resting/ramified to phagocytic/amoeboid phenotype.
Keratan sulfate, recognized by the antibody clone 5D4 (5D4 KS), represents a promising surface marker for the study of microglia resting state, even if its biological significance has not been explored. The correlation between the resting state of microglia and the expression of 5D4 KS is suggested by the alteration of 5D4KS expression from the cell surface when microglia is activated after neuronal injury in rodents.
Our hypothesis postulate that 5D4 KS expressing cells represent a resting functional state able to confer to microglia the capability to act as a sentinels for external insults, and that, after injury occurs in MS, the loss of 5D4 KS lead to the acquisition of activated phenotype.
We used immunohistochemistry analysis to characterize the 5D4 KS in human post-mortem brain tissues obtained from control and MS subjects. We analyzed its presence in lesions (i.e. pre-active, active, chronic active) of white (WM) and grey (GM) matter, and in normal appearing WM and GM. Furthermore, with a combined immunofluorescence analysis, we discriminated 5D4 KS in cellular subpopulations (i.e. ramified or activated microglia, astrocytes, oligodendrocytes, neurons and inflammatory infiltrating cells). In addition, we characterized 5D4 KS expression in whole murine CNS under physiological conditions.
First, we detected 5D4KS in human MS brains. Particularly, we identified 5D4KS in ramified cells in a specific WM site near to the lesions. Then, in mouse CNS, we observed for the first time 5D4 KS at a basal level, particularly in hippocampus and striatum. Here, we identified 5D4 KS in Iba1 expressing cells. In addition, the morphology of all 5D4 KS expressing cells is similar to ramified microglia cells.
These data suggest that there are different subtypes of microglial cells assuming specific phenotypes and/or functional states. Particularly, 5D4KS could represent a marker of ramified microglia expressed by cells in injured MS human brain.
Disclosure:
Montarolo Francesca: nothing to disclose
Perga Simona: nothing to disclose
Bono Gabriele: nothing to disclose
Bonaldo Brigitta: nothing to disclose
Martire Serena: nothing to disclose
Bertolotto Antonio: nothing to disclose
Abstract: EP1414
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Inflammation and tissue damage
Microglia constitute the population of resident tissue macrophages in the central nervous system (CNS) and are critically involved in the pathogenesis of Multiple Sclerosis (MS). Particularly, all MS brain lesions are associated with the presence of activated microglia but their activation mechanism remains elusive. Mainly, in response to a variety of stimuli, microglia up- or down-regulate surface molecule in order to undergo morphological transformation from resting/ramified to phagocytic/amoeboid phenotype.
Keratan sulfate, recognized by the antibody clone 5D4 (5D4 KS), represents a promising surface marker for the study of microglia resting state, even if its biological significance has not been explored. The correlation between the resting state of microglia and the expression of 5D4 KS is suggested by the alteration of 5D4KS expression from the cell surface when microglia is activated after neuronal injury in rodents.
Our hypothesis postulate that 5D4 KS expressing cells represent a resting functional state able to confer to microglia the capability to act as a sentinels for external insults, and that, after injury occurs in MS, the loss of 5D4 KS lead to the acquisition of activated phenotype.
We used immunohistochemistry analysis to characterize the 5D4 KS in human post-mortem brain tissues obtained from control and MS subjects. We analyzed its presence in lesions (i.e. pre-active, active, chronic active) of white (WM) and grey (GM) matter, and in normal appearing WM and GM. Furthermore, with a combined immunofluorescence analysis, we discriminated 5D4 KS in cellular subpopulations (i.e. ramified or activated microglia, astrocytes, oligodendrocytes, neurons and inflammatory infiltrating cells). In addition, we characterized 5D4 KS expression in whole murine CNS under physiological conditions.
First, we detected 5D4KS in human MS brains. Particularly, we identified 5D4KS in ramified cells in a specific WM site near to the lesions. Then, in mouse CNS, we observed for the first time 5D4 KS at a basal level, particularly in hippocampus and striatum. Here, we identified 5D4 KS in Iba1 expressing cells. In addition, the morphology of all 5D4 KS expressing cells is similar to ramified microglia cells.
These data suggest that there are different subtypes of microglial cells assuming specific phenotypes and/or functional states. Particularly, 5D4KS could represent a marker of ramified microglia expressed by cells in injured MS human brain.
Disclosure:
Montarolo Francesca: nothing to disclose
Perga Simona: nothing to disclose
Bono Gabriele: nothing to disclose
Bonaldo Brigitta: nothing to disclose
Martire Serena: nothing to disclose
Bertolotto Antonio: nothing to disclose