Interaction of T lymphocytes and macrophages with cultured vascular endothelial cells: Attachment, invasion, and subsequent degradation of the subendothelial extracellular matrix

Abstract

Circulating macrophages and T lymphocytes can invade the vascular endothelium and migrate from the circulatory system to an extravascular compartment such as inflammatory organs. In an in vitro model system we have examined the capacity of murine T lymphocytes and peritoneal macrophages to attach and invade a confluent vascular endothelial cell monolayer and to degrade sulfated proteoglycans in the subendothelial extracellular matrix. Concanavalin A and antigen-specific (egg albumin) activated T lymphocytes labeled with [³H]thymidine attached to the apical surface of the vascular endothelium in a time-dependent manner. A subsequent invasion of the endothelial cell monolayer was observed by scanning electron microscopy. Both activated T lymphocytes and murine macrophages degraded the [³⁵S]O₄=-containing fragments in a process which required cell-matrix contact but was not dependent on serum proteases. Sulfated glycosaminoglycan chains produced from matrix proteoglycans by treatment with papain or alkaline borohydride were 3–4 times larger than the cell-mediated degradation fragments. This suggests that both macrophages and T lymphocytes elaborate upon stimulation an endoglicosidase capable of cleaving glycosaminoglycans specifically and releasing heparan sulfate-rich fragments. The ability of activated cells of the immune system to attach and invade the vascular endothelium and to degrade sulfated proteoglycans is very similar to that reported for highly metastatic tumor cells.