Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (JAM)

doi:10.1084/jem.190.9.1351

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© The Rockefeller University Press, 0022-1007/1999/11/1351/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 9, November 1, 1999 1351-1356

Brief Definitive Reports

Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (JAM)

Aldo Del Maschio^a, Ada De Luigi^a, Ines Martin-Padura^a, Manfred Brockhaus^e, Tamas Bartfai^e, Paolo Fruscella^a, Luciano Adorini^c, GianVito Martino^b, Roberto Furlan^b, Maria Grazia De Simoni^a, and Elisabetta Dejana^a,d
^a Istituto di Ricerche Farmacologiche "Mario Negri, " 20157 Milan, Italy
^b DIBIT, 20132 Milan, Italy
^c Roche Milano Ricerche, 20132 Milan, Italy
^d Universita' degli Studi dell'Insubria, Dipartimento di Scienze Cliniche e Biologiche, Facolta' di Medicina e Chirurgia, 21100 Varese, Italy
^e F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland

Correspondence to: Elisabetta Dejana, Istituto di Ricerche Farmacologiche “Mario Negri,” Via Eritrea 62, 20157 Milano, Italy. Tel:39-02-390141 Fax:39-02-3546277 E-mail:dejana{at}irfmn.mnegri.it.

The mechanisms that govern leukocyte transmigration throughthe endothelium are not yet fully defined. Junctional adhesionmolecule (JAM) is a newly cloned member of the immunoglobulinsuperfamily which is selectively concentrated at tight junctionsof endothelial and epithelial cells. A blocking monoclonal antibody(BV11 mAb) directed to JAM was able to inhibit monocyte transmigrationthrough endothelial cells in in vitro and in vivo chemotaxisassays. In this study, we report that BV11 administration wasable to attenuate cytokine-induced meningitis in mice. The intravenousinjection of BV11 mAb significantly inhibited leukocyte accumulationin the cerebrospinal fluid and infiltration in the brain parenchyma.Blood–brain barrier permeability was also reduced by themAb. We conclude that JAM may be a new target in limiting theinflammatory response that accompanies meningitis.

Key Words: endothelium, tight junction, meningitis, vascular permeability,blood–brain barrier

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