Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM).
The mechanisms that govern leukocyte transmigration through the endothelium are not yet fully defined. Junctional adhesion molecule (JAM) is a newly cloned member of the immunoglobulin superfamily which is selectively concentrated at tight junctions of endothelial and epithelial cells. A blocking monoclonal antibody (BV11 mAb) directed to JAM was able to inhibit monocyte transmigration through endothelial cells in in vitro and in vivo chemotaxis assays. In this study, we report that BV11 administration was able to attenuate cytokine-induced meningitis in mice. The intravenous injection of BV11 mAb significantly inhibited leukocyte accumulation in the cerebrospinal fluid and infiltration in the brain parenchyma. Blood-brain barrier permeability was also reduced by the mAb. We conclude that JAM may be a new target in limiting the inflammatory response that accompanies meningitis.
Del Maschio
A
A
Istituto di Ricerche Farmacologiche "Mario Negri, " 20157 Milan, Italy.
De Luigi
A
A
Martin-Padura
I
I
Brockhaus
M
M
Bartfai
T
T
Fruscella
P
P
Adorini
L
L
Martino
G
G
Furlan
R
R
De Simoni
M G
MG
Dejana
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D062726:Junctional Adhesion Molecules; D007962:Leukocytes / Q000276:immunology*; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000276:immunology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D062726:Junctional Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha