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 e...

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Bibliographic Details
Published in:European journal of immunology 2003-02, Vol.33 (2), p.402-410
Main Authors: Crane, Isabel J, Xu, Heping, Manivannan, Ayyakkannu, McKillop-Smith, Susan, Lamont, Graeme, Wallace, Carol, Liversidge, Janet, Sharp, Peter F, Forrester, John V
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Autoimmune Diseases - immunology
Autoimmune Diseases - physiopathology
Blood-Retinal Barrier
Cell Adhesion - drug effects
Chemokine CCL3
Chemokine CCL4
Chemotaxis, Leukocyte - drug effects
Disease Progression
Endothelium, Vascular - pathology
Female
Hemorheology
Lasers
Leukocyte Rolling - drug effects
Leukocytes - drug effects
Leukocytes - physiology
Macrophage Inflammatory Proteins - antagonists & inhibitors
Macrophage Inflammatory Proteins - immunology
Macrophage Inflammatory Proteins - physiology
Mice
Microscopy, Confocal
Ophthalmoscopes
Ophthalmoscopy - methods
Retinitis - immunology
Retinitis - physiopathology
Uveitis - immunology
Uveitis - physiopathology
Venules
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Summary: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.
ISSN:0014-2980