Physically damaged extracellular matrix induces TNF-alpha secretion by interacting resting CD4+ T cells and...

T lymphocytes and macrophages (Mø) are seen to accumulate at sites of lesions in blood vessel walls, suggesting that these cells may contribute to the initiation of the local inflammatory reaction. Tumour necrosis factor-alpha (TNF-alpha), a cytokine produced by both cell types, plays a major role in inflammatory reactions, in blood vessel formation, in thrombosis and in atherosclerosis. We now report that secretion of TNF-alpha by CD4+ T cells and Mø can be induced in vitro in the absence of antigen, in an MHC-II-independent manner by immobilized extracellular matrix (ECM). Moreover, the level of TNF secretion is greatly enhanced in the presence of physically damaged ECM (dECM). This mode of TNF secretion is regulated primarily by the fibronectin or laminin glycoprotein components of ECM. Thus, a multicellular interaction with ECM proteins exposed as a consequence of vascular wall injury can serve to signal the secretion of TNF-alpha by both cell types which induces the recruitment of additional immune cells to the developing lesion.