Pathways and bottlenecks in the web of inflammatory adhesion molecules andchemoattractants

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