Astrocytes specifically remove surface-adsorbed fibrinogen and locally express chondroitin sulfate proteoglycans

Abstract

Surface-adsorbed fibrinogen (FBG) was recognized by adhering astrocytes and removed from the substrates in vitro by a two-phase removal process. The cells removed adsorbed FBG from binary proteins surface patterns (FBG + laminin, or FBG + albumin) while leaving the other protein behind. Astrocytes preferentially expressed chondroitin sulfate proteoglycan (CSPG) at the loci of fibrinogen stimuli; however no differences in overall CSPG production as a function of FBG surface coverage were identified. Removal of FBG by astrocytes was also found to be independent of transforming growth factor type β (TGF-β) receptor based signaling as cells maintained CSPG production in the presence of TGF-β receptor kinase inhibitor, SB 431542. The inhibitor decreased CSPG expression, but did not abolicsh it entirely. Because blood contact and subsequent FBG adsorption are unavoidable in neural implantations, the results indicate that implant-adsorbed FBG may contribute to reactive astrogliosis around the implant as astrocytes specifically recognize adsorbed FBG.

Fibrin(ogen) and neurodegeneration in the progressive multiple sclerosis cortex

“…22,23 Regardless, our findings challenge the idea that large-molecular-weight serum proteins are not deposited in the progressive MS cortex. Fibrin(ogen) was located in both the extracellular space and within cells and intracellular processes with varying distributions.…”

Astrocytes alignment and reactivity on collagen hydrogels patterned with ECM proteins

“…No changes in the protein pattern appearance were observed over that time period. Unlike the removal of glass-adsorbed fibrinogen by astrocytes seen previously [43], proteins patterned on collagen were not removed by cells over the given culture time period. We infer that the protocol used created stable, immobilized protein patterns that did not diffuse into the gel or desorb/detach from the collagen surface.…”

“…We have previously seen that adsorbed FBG was removed from glass surfaces below adhered astrocytes, most likely because of the protein was simply adsorbed to the surface [43]. In the case of immobilized FBG on collagen gel surface, astrocytes did not remove fibrinogen or any of the other three ECM proteins from the surface, indicating that the transfer procedure created stable crosslinks between the protein molecules and the gel surface.…”

“…Although some variants of the chondroitin sulfate (CS) chains, such as CS-C, are inhibitory to neuronal outgrowth and others variants (CS-A and CS-E) are not [45], astrocyte expression of CSPG is correlated with their inhibitive properties to neurons. While CSPG are also shed into the surrounding cellular environment by astrocytes [43,45], the surface expression on their membranes is important for interfacing with neurons. It is therefore informative to determine if a CNS biomaterial scaffold itself is increasing astrocyte surface expression of CSPG.…”

Mechanical disruption of the blood–brain barrier following experimental concussion

“…Surprisingly, there was minimal uptake of serum proteins by microglia when compared with astrocytes and neurons, which may reflect cell-specific uptake for the clearance of serum proteins after TBI. Notably, astrocytes have previously been demonstrated to selectively clear FBG in vitro [38]. Since neurons staining for FBG following concussion appeared morphologically normal at the time points examined in the present study, further temporal studies would be required to examine if this uptake has pathological consequences.…”