The effect of genetic deficiency of adhesion molecules on the course of endotoxin-induced uveitis.
OBJECTIVE
Multiple adhesion molecules of the selectin, integrin, and immunoglobulin-like families are involved in the migration of leukocytes out of the bloodstream into inflamed tissues. This study addresses the question of which adhesion molecules are specifically involved in endotoxin-induced uveitis.


METHODS
Mice genetically deficient in p-selectin, ICAM-1, beta2-integrin, or controls received intravitreal injections of endotoxin. Eyes were harvested 24 h later and inflammation was evaluated by histologic and immunohistochemical assays of infiltrating cells.


RESULTS
Mice lacking either P-selectin or beta2-integrin had less inflammation than controls (median cells/section: 64 for P-selectin knockout vs 130 for controls, p=0.02, n=17 per group: 244 for beta2-integrin knockouts, n=14, vs 355 for controls, n=17, p=0.05). Neither gene deletion significantly changed the ratio of infiltrating neutrophils to macrophages. ICAM-1 knockouts tended to have fewer infiltrating cells (median 22 cells/section) compared to controls (median 132 cells/section), but this difference was not statistically significant (p=0.25, n=9 per group).


CONCLUSIONS
P-selectin, beta2-integrin, and possibly ICAM-1 are involved in the ocular inflammatory response to endotoxin. The lack of complete inhibition of leukocyte infiltration with the complete loss of each adhesion molecule is in accord with the notion that alternative adhesion molecules also participate in this process.
Planck
S R
SR
Casey Eye Institute, Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201-4197, USA. plancks@ohsu.edu
Han
Y B
YB
Park
J M
JM
O'Rourke
L
L
Gutierrez-Ramos
J C
JC
Rosenbaum
J T
JT
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism*; D002924:Ciliary Body / Q000378:metabolism; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D017353:Gene Deletion; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
D018821:CD18 Antigens; D004731:Endotoxins; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1