Emerging functions of thrombospondin-1 in immunity

Thrombospondin-1 is a secreted matricellular glycoprotein that modulates cell behavior by interacting with components of the extracellular matrix and with several cell surface receptors. Its presence in the extracellular matrix is induced by injuries that cause thrombospondin-1 release from platelets and conditions including hyperglycemia, ischemia, and aging that stimulate its expression by many cell types. Conversely, rapid receptormediated clearance of thrombospondin-1 from the extracellular space limits its sustained presence in the extracellular space and maintains sub-nanomolar physiological concentrations in blood plasma. Roles for thrombospondin-1 signaling, mediated by specific cellular receptors or by activation of latent TGF13, have been defined in T and B lymphocytes, natural killer cells, macrophages, neutrophils, and dendritic cells. In addition to regulating physiological nitric oxide signaling and responses of cells to stress, studies in mice lacking thrombospondin-1 or its receptors have revealed important roles for thrombospondin-1 in regulating immune responses in infectious and autoimmune diseases and antitumor immunity.

Automated summary

Thrombospondin-1 modulates cell behavior by interacting with components of the extracellular matrix and cell surface receptors. Its release and expression are influenced by injuries and various diseases, while its sustained presence in the extracellular space is regulated by receptor-mediated clearance. Thrombospondin-1 plays important roles in immune responses.