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.
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1 November 1999
Brief Definitive Report|
November 01 1999
Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (Jam)
Aldo Del Maschio,
Aldo Del Maschio
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
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Ada De Luigi,
Ada De Luigi
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
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Ines Martin-Padura,
Ines Martin-Padura
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
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Manfred Brockhaus,
Manfred Brockhaus
eF. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland
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Tamas Bartfai,
Tamas Bartfai
eF. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland
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Paolo Fruscella,
Paolo Fruscella
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
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Luciano Adorini,
Luciano Adorini
cRoche Milano Ricerche, 20132 Milan, Italy
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GianVito Martino,
GianVito Martino
bDIBIT, 20132 Milan, Italy
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Maria Grazia De Simoni,
Maria Grazia De Simoni
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
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Elisabetta Dejana
Elisabetta Dejana
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
dUniversita' degli Studi dell'Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facolta' di Medicina e Chirurgia, 21100 Varese, Italy
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Aldo Del Maschio
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
Ada De Luigi
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
Ines Martin-Padura
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
Manfred Brockhaus
eF. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland
Tamas Bartfai
eF. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland
Paolo Fruscella
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
Luciano Adorini
cRoche Milano Ricerche, 20132 Milan, Italy
GianVito Martino
bDIBIT, 20132 Milan, Italy
Roberto Furlan
bDIBIT, 20132 Milan, Italy
Maria Grazia De Simoni
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
Elisabetta Dejana
aIstituto di Ricerche Farmacologiche “Mario Negri, ” 20157 Milan, Italy
dUniversita' degli Studi dell'Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facolta' di Medicina e Chirurgia, 21100 Varese, Italy
Received:
February 21 1999
Revision Requested:
July 15 1999
Accepted:
July 27 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (9): 1351–1356.
Article history
Received:
February 21 1999
Revision Requested:
July 15 1999
Accepted:
July 27 1999
Citation
Aldo Del Maschio, Ada De Luigi, Ines Martin-Padura, Manfred Brockhaus, Tamas Bartfai, Paolo Fruscella, Luciano Adorini, GianVito Martino, Roberto Furlan, Maria Grazia De Simoni, Elisabetta Dejana; Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (Jam). J Exp Med 1 November 1999; 190 (9): 1351–1356. doi: https://doi.org/10.1084/jem.190.9.1351
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