EXTRACELLULAR-MATRIX HEPARAN-SULFATE MODULATES ENDOTHELIAL-CELL SUSCEPTIBILITY TO STAPHYLOCOCCUS-AUREUS

The ability of extracellular matrix heparan sulfate to alter the susce ptibility of human endothelial cells to S. aureus was investigated. En dothelial cells grown on extracellular matrix synthesized by S. aureus -infected endothelial cells were more susceptible to subsequent staphy lococcal infection than endothelial cells grown on the extracellular m atrix synthesized by untreated endothelial cells. Endothelial cells we re more susceptible to S. aureus infection when 1) grown on heparitina se-treated extracellular matrix that removed heparan sulfate chains, 2 ) grown on extracellular matrix produced by chlorate-treated endotheli al cells that reduced sulfation in the matrix heparan sulfate proteogl ycans, 3) grown on heparan sulfate purified from extracellular matrix elaborated by infected endothelial cells, and 4) endothelial cells wer e chlorate-treated and therefore expressed desulfated cellular heparan sulfate proteoglycans. Extracellular matrix produced by S. aureus-inf ected endothelial cells contained heparan sulfate proteoglycans With r educed sulfation. The altered extracellular matrix with reduced sulfat ed heparan sulfate proteoglycans signalled the uninfected endothelial cells to produce under sulfated cellular heparan sulfate proteoglycans that increased S. aureus adherence to the endothelial cells. (C) 1997 Wiley-Liss, Inc.