Inhibition of Monocyte/Macrophage Migration to a Spinal Cord Injury Site by an Antibody to the Integrin αD: A Potential New Anti-inflammatory Treatment

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. β2 integrins play an essential role in leukocyte trafficking and activation and arbitrate cell–cell interactions during inflammation. The β2 integrin, αDβ2, 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 αDβ2 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 αD subunit would reduce the inflammatory response after a spinal cord transection injury in rats. At a 1 mg/kg dose two of three anti-αD mAbs caused a significant (∼65%) reduction in the number of macrophages at the injury site and one anti-αD mAb led to a ∼43% reduction in the number of neutrophils at the SCI site. Thus, our results support the concept that the αDβ2 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-αD mAbs can reduce the extravasation of macrophages and, to a lesser extent, neutrophils, to the SCI site.