Macrophage depletion prevents leukocyte adhesion and disease induction in experimental melanin-protein induced uveitis

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Item Type:	Article
Title:	Macrophage depletion prevents leukocyte adhesion and disease induction in experimental melanin-protein induced uveitis
Creators Name:	Baatz, H., Puchta, J., Reszka, R. and Pleyer, U.
Abstract:	The purpose was to study the effects of macrophage depletion with liposomal dichloromethylene-diphosphonate (Cl2MDP-lip) on inflammation and leukocyte-endothelium interaction in experimental melanin-protein induced uveitis (EMIU). Lewis rats (n = 48) were immunized with melanin-associated protein in complete Freund's adjuvant and pertussis toxin. Control groups received adjuvants without the antigen (n = 12) or no injection (n = 6). Animals received treatment with either CL2MDP-lip or empty liposomes (empty-lip) on day -2, 1, 4, 6 and 8. Leukocytes were stained with rhodamine 6G i.v. and intravital fluorescence microscopy (IVM) was performed on day 4, 6, 8 and 10 to quantify leukocyte rolling and arrest. After IVM, the cell count and protein concentration were determined in aqueous humor and plasma levels of TNF-α and IFN-γ were measured by ELISA. In EMIU, leukocyte rolling increased on day 4 (10.0 ± 1.2 cells min-1 vs baseline of 5.7 ± 0.7 cells min-1, mean ± S.E.(M.)) and peaked on day 8 (40.8 ± 4.2 cells min-1; P ≤ 0.05). Leukocyte arrest was increased on day 8 (175.4 ± 18.2 cells mm-2 vs baseline of 59.7 ± 7.1 cells mm-2; P ≤ 0.05) and day 10 (371.7 ± 30.7 cells mm-2). CL2MDP-lip prevented leukocyte rolling (day 10: 16.6 ± 1.8 cells min-1 vs 30.7 ± 2.9 cells min-1; CL2MDP-lip vs untreated EMIU; P ≤ 0.05) and arrest (day 8: 88.3 ± 13 cells mm-2: day 10: 128.5 ± 12.9 cells mm-2; P ≤ 0.05). Empty-lip had no effect on leukocyte rolling (day 10: 34.8 ± 4.2 cells min-1) or arrest (day 8: 159.3 ± 12.9 cells mm-2, day 10: 421.2 ± 41.6 cells mm-2). CL2MDP-lip completely suppressed leukocyte emigration (11 ± 2 cells μl-1 vs 100 ± 29 cells μ-1; CL2MDP-lip vs empty-lip; P ≤ 0.05) and protein extravasation into aqueous humor (2.7 ± 0.3 mg ml-1 vs 14.2 ± 2.1 mg ml-1; CL2MDP-lip vs empty-lip; P ≤ 0.05), abrogated the TNF-α response (32.5 ± 2.7 pg ml-1 vs 954.9 ± 216.3 pg ml-1: CL2MDP-lip vs untreated EMIU: P ≤ 0.05) and caused an attenuated and delayed elevation of IFN-γ. CL2MDP-lip prevented the inflammatory reaction of EMIU and inhibited the increase of leukocyte-endothelium interaction in iris vessels. Our findings emphasize the pivotal role macrophages play in the initiation of autoimmune disease.
Keywords:	Cell Adhesion, Clodronate, Experimental Melanin-Protein Induced Uveitis, Immunoregulation, Leukocyte-Endothelium Interaction, Macrophages, Microcirculation
Source:	Experimental Eye Research
ISSN:	0014-4835
Publisher:	Academic Press
Volume:	73
Number:	1
Page Range:	101-109
Date:	1 January 2001
Official Publication:	https://doi.org/10.1006/exer.2001.1016
PubMed:	View item in PubMed

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