title: Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment.
abstract: The inflammatory response that ensues during the initial 48 to 72 h after spinal cord injury causes considerable secondary damage to neurons and glia. Infiltration of proinflammatory-activated neutrophils and monocytes/macrophages into the cord contributes to spinal cord injury-associated secondary damage. beta2 integrins play an essential role in leukocyte trafficking and activation and arbitrate cell-cell interactions during inflammation. The beta2 integrin, alphaDbeta2, is expressed on monocytes/macrophages and neutrophils and binds to vascular adhesion molecule-1 (VCAM-1). The increased expression of VCAM-1 during central nervous system (CNS) inflammation likely contributes to leukocyte extravasation into the CNS. Accordingly, blocking the interaction between alphaDbeta2 and VCAM-1 may attenuate the inflammatory response at the SCI site. We investigated whether the administration of monoclonal antibodies (mAbs) specific for the rat alphaD subunit would reduce the inflammatory response after a spinal cord transection injury in rats. At a 1 mg/kg dose two of three anti-alphaD mAbs caused a significant ( approximately 65%) reduction in the number of macrophages at the injury site and one anti-alphaD mAb led to a approximately 43% reduction in the number of neutrophils at the SCI site. Thus, our results support the concept that the alphaDbeta2 integrins play an important role in the trafficking of leukocytes to a site of central nervous system inflammation. This study also offers preliminary evidence that anti-alphaD mAbs can reduce the extravasation of macrophages and, to a lesser extent, neutrophils, to the SCI site.
authors.affiliation: The Neurodegeneration Research Group, The John P. Robarts Research Institute, London, Ontario, N6A 5K8, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mabon
authors.forename: L C
authors.initials: LC
authors.lastname: Weaver
authors.forename: G A
authors.initials: GA
authors.lastname: Dekaban
mesh_terms: D000818:Animals; D018845:CD11 Antigens; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D039001:Integrin alpha Chains; D016023:Integrins / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009187:Myelitis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D016024:Receptors, Cytoadhesin; D013119:Spinal Cord Injuries / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
chemical_list: D018845:CD11 Antigens; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D016023:Integrins; D016024:Receptors, Cytoadhesin; D019010:Vascular Cell Adhesion Molecule-1; D008775:Methylprednisolone