Sialyl ligands facilitate lymphocyte accumulation during inflammation of the central nervous system

Combined models of cytokine-induced inflammation in the skin and spinal cord of the rat were utilised to demonstrate in vivo that circulating lymphocytes depend upon sialylated adhesion molecules on their surface for maximal recruitment into inflammatory sites in both tissues. When radiolabelled normal spleen cells were incubated with sialidase from Vibrio cholerae or Clostridium perfringens, or with the specific sialic acid-binding lectin from Limax flavus, prior to being washed and injected intravenously into rats, they accumulated significantly less than untreated control cells into tumor necrosis factor (TNF)-activated spinal cord and skin. Pretreatment of splenocytes with sialidase plus the competitive inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DDN) partially restored the accumulation of radiolabelled cells at both inflammatory sites, providing evidence for the specificity of sialidase treatment and the importance of sialyl residues. Pretreatment of macrophage-depleted spleen lymphocytes, or ovalbumin-specific W3/25+ (CD4) cell line T lymphocytes with sialidase produced similar decrements in accumulation at inflammatory sites, demonstrating that lymphocytes, including memory T cells, were relying on sialyl ligands for maximal recruitment. Results from this in vivo study are interpreted as providing indirect evidence that inducible sialyl-binding molecules, probably of the 'selectin' type, occur to a functionally significant extent on activated central nervous system (CNS) endothelium. We speculate that such carbohydrate-binding adhesion molecules may play an important role in the recruitment of inflammatory cells during the formation of CNS lesions in diseases such as the encephalomyelitides and multiple sclerosis.