TY - JOUR
T1 - Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants
AU - Ley, Klaus
N1 - Funding Information:
I would like to thank Dan C. Bullard and Geoff S. Kansas for valuable discussions that ultimately led to the development of the web model of pathways and bottlenecks. The original research underlying this review was supported by NIH R01 HL 54136 and HL 64381.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Chemokines
KW - Inflammation
KW - Integrins
KW - Neutrophils
KW - Selectins
UR - http://www.scopus.com/inward/record.url?scp=0034952240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034952240&partnerID=8YFLogxK
U2 - 10.1385/IR:24:1:87
DO - 10.1385/IR:24:1:87
M3 - Article
C2 - 11485212
AN - SCOPUS:0034952240
SN - 0257-277X
VL - 24
SP - 87
EP - 95
JO - Immunologic Research
JF - Immunologic Research
IS - 1
ER -