Effect of anti-macrophage inflammatory protein-1alpha on leukocyte trafficking and disease progression in experimental autoimmune uveoretinitis.
This study has enabled us to identify the influence of the chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha), on leukocyte behavior at the blood-retina barrier in vivo and its link with the inflammatory process and disease pathogenesis. MIP-1alpha has not previously been thought to be effective under conditions of physiological shear flow. However, short-term anti-MIP-1alpha treatment inhibited leukocyte slowing and accumulation and subsequent extravasation of leukocytes at the blood-retina barrier in animals with experimental autoimmune uveoretinitis. This was effective predominantly in the post-capillary venules which have been shown to be the main site of passage of leukocytes across the blood-retina barrier. Long-term anti-MIP-1alpha treatment also prevented decreased leukocyte velocity and reduced disease severity as measured clinically, histologically and in terms of blood-retina barrier breakdown.
Crane
Isabel J
IJ
Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen, GB. i.j.crane@abdn.ac.uk
Xu
Heping
H
Manivannan
Ayyakkannu
A
McKillop-Smith
Susan
S
Lamont
Graeme
G
Wallace
Carol
C
Liversidge
Janet
J
Sharp
Peter F
PF
Forrester
John V
JV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D001813:Blood-Retinal Barrier; D002448:Cell Adhesion / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D018056:Hemorheology; D007834:Lasers; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D019721:Ophthalmoscopes; D009887:Ophthalmoscopy / Q000379:methods; D012173:Retinitis / Q000276:immunology* / Q000503:physiopathology; D014605:Uveitis / Q000276:immunology* / Q000503:physiopathology; D014699:Venules
D000911:Antibodies, Monoclonal; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins