Basement membrane proteins in multiple sclerosis-associated inflammatory cuffs:: Potential role in influx and transport of leukocytes

Perivascular accumulation of macrophages and lymphocytes is a prominent feature of multiple sclerosis (MS) pathology. To enter the brain parenchyma, immune cells need to migrate across the blood-brain barrier through a number of well-defined processes. So far, little attention has been given to the role of the basement membrane (BM) in leukocyte recruitment into the central nervous system (CNS). Here, we characterized the molecular composition of the vascular and astroglial BMs in chronic active and active MS lesions with large perivascular infiltrates using antibodies directed against several extracellular matrix (ECM) proteins. A differential expression of specific laminin chains in vascular and astroglial BMs was observed. Interestingly, we found fiber-like depositions of ECM within inflammatory cuffs. These structures were immunopositive for several laminin isoforms, fibronectin, collagen IV, and heparan sulfate proteoglycans. Strikingly, we observed myelin-laden macrophages in the Virchow-Robin space. Because BM molecules are in close contact with these cells, we postulate that BM proteins within inflammatory cuffs may serve as a conduit network and therefore facilitate the transport of myelin-containing phagocytes out of the CNS toward peripheral lymph nodes.