Provide a link between selectin-mediated cell adhesion and chemokine-induced cellular activation and accelerate the progression of leukocyte infiltration in renal inflammation. They also demonstrated a direct LDN-193189 interaction of collagen XVIII HS side chains with L-selectin and MCP-1 in vitro. Others showed the interaction of proteoglycans with the leukocyte adhesion molecules MAC-1 and VLA-4. We confirmed here the direct interaction between L-selectin and the tubular BMspecific short collagen XVIII molecule. Furthermore, we showed that the long HS chains within N-terminal non-collagenous portion of this particular isoform contain HS domains that can interact with L-selectin. This interaction indicates the involvement of collagen XVIII GAG chains in leukocyte adhesion and migration via interaction with L-selectin, and can at least partly explain less influx of inflammatory cells in collagen XVIII deficient mice. Third, proteoglycans are known to stabilize gradients of chemokines and cytokines. As shown by Celie et al., binding sites for MCP-1, a potent chemoattractant for monocytes/ macrophages, were increased after I/R and are predominantly mediated by HSPGs in BM. Our data confirms the involvement of collagen XVIII GAG side chains in chemokinederived leukocyte migration and solid phase binding assay showed the binding of collagen XVIII to MCP-1 via its GAG chains. The binding appeared to be stronger when the GAG side chains attached to collagen XVIII were longer indicating that certain HS domains/length of collagen XVIII are needed to efficiently bind this chemokine. Moreover involvement of specific GAG side chains of collagen XVIII in chemokine-induced leukocyte migration was confirmed by the significant increase in monocyte migration over filters coated with N-terminal fragment with longest GAG chains compared to filters coated with N-terminal fragments without GAG chains. Since the Coll XVIII Tsp1-C18 fragment has one predicted GAG attachment site, we assume that fraction 32–34 of the collagen XVIII Tsp1-C18 fragment has HS-GAG chains of intermediate length. However, we cannot exclude the possibility that these fractions with shorter HSGAG side chain were decorated with different sulfation pattern that will influence L-selectin and MCP-1 binding and leukocyte migration. We show an increase in expression of MCP-1 in renal tissue of double collagen deficient mice at the same timepoint that the animals show the lowest influx of the cells. Our results show that even increased expression of MCP-1 does not lead to higher inflammatory cells influx if the BM HSPGs are absent. These findings highlight the importance of the interaction between collagen XV and XVIII and chemokines such as MCP-1 in cell influx. Since the two BM collagens type XV and XVIII have some similarities, including the Tsp-1 domain at the N-terminus and the GAG side chains, we speculate that lacking both of those BM zone collagen.