Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants

Leukocyte recruitment requires capture, rolling, activation, adhesion, and transmigration. Adhesion molecules and chemoattractants have been identified that mediate each of these steps. Their functions often overlap, but the combined absence of some molecules can lead to severe spontaneous phenotypes, as seen in CD18-/- mice, or early lethality, as in CD18-/- E-selectin-/- mice. These groups of molecules define bottlenecks that restrict the inflammatory response. Adhesion molecules and activation mechanisms can also form groups of preferential usage, or pathways. Based on these findings, a web-like model may represent the inflammatory process better than the linear cascade model. Bottlenecks and pathways depend on the degree and nature of overlapping functions, the disease process, tissue site, and the inflammatory stimulus.