Abstract
In order to understand a mechanism of monocyte-endothelial cell interactions, the present study was performed to investigate the degradation of sulfated proteoglycans in the subendothelial extracellular matrix (ECM) by monocytemacrophages in vitro. Adherent mononuclear leucocytes isolated from human peripheral blood were plated on the [35S]O4-prelabeled ECM coated dishes prepared from cultured porcine aortic endothelial cells. The nature of radiolabeled materials released upon incubation of the ECM with cells at 37°C for 48-72hrs was studied by applying the culture medium to gel filtration on Sepharose CL-6B columns. The monocyte-macrophages solubilized the labeled matrix to a lower mol, wt. component compared with the material released during exposure of the ECM to medium without cells that eluted with the void volume. Degradation products eluted in the lower mol. wt. peak were precipitated with cetylpyridinium chloride and were resistant to further digestion with alkali, pronase or chondroitin ABC lyase, but were converted to further lower mol, wt. fragments after nitrous acid or heparitinase treatment. The size of intact glycosaminoglycan side chains determined by subjecting the ECM to cleavage with alkali or pronase was larger than that of degradation products released by the cells. Heparin inhibited the degrading activity of cells.
These results suggest that the attachment and subsequent invasion of vascular endothelium by monocyte-macrophages may involve the production of ECM heparan sulfate degrading activity by these cells.
