Figure 7.

The recognition of bacteria and viruses in the lungs results in the activation of Toll-like receptor (TLR) signalling pathways, which leads to pulmonary inflammation and under ideal conditions the clearance of the pathogen. Proteoglycans and/or their glycosaminoglycans modify the inflammatory response in lungs through a number of different mechanisms. (1) The release of soluble proteoglycans such as biglycan or degradation of glycosaminoglycan such as hyaluronan and heparan sulfate can activate TLRs. (2) Cytokines, chemokines, and growth factors bind to glycosaminoglycans, which can either increase or decrease their biological activity. (3) Adhesion molecules including the selectins, integrins, and CD44 bind to proteoglycans and glycosaminoglycan, which suggests that these proteins play a critical role in leukocyte adhesion and migration. (4) Chemokine-glycosaminoglycan interactions provide fine-tune control of chemokine-gradient formation and leukocyte migration in tissue. (5) Activation of stromal and immune cells results in the release of MMP. Growing evidence shows that interactions between proteoglycans and MMPs play important roles in the regulation of the innate immune response. (6) Degradation of proteoglycans by MMPs and other proteases controls the amount and localization of proteoglycans in lungs. In addition, proteolytic cleavage of proteoglycans leads to the unmasking of cryptic fragments.