Human Spinal Cord Injury Causes Specific Increases in Surface Expression of Beta Integrins on Leukocytes

Abstract

Spinal cord injury (SCI) activates circulating leukocytes that migrate into the injured cord and bystander organs using adhesion molecule-mediated mechanisms. These cells cause oxidative damage, resulting in secondary injury to the spinal cord, as well as injury to bystander organs. This study was designed to examine, over a 6-h to 2-week period, changes in adhesion molecule surface expression on human peripheral leukocytes after SCI (9 subjects), using as controls 10 uninjured subjects and 6 general trauma patients (trauma controls, TC). Both the percentage of cells expressing a given adhesion molecule and the average level of its expression was quantified for both circulating neutrophils and monocytes. The percentage of neutrophils and monocytes expressing the selectin CD62L was unchanged in TC and SCI patients after injury compared to uninjured subjects. Concurrently, the amount of surface CD62L on neutrophils was decreased in SCI and TC subjects, and on monocytes after SCI. The percentage of neutrophils expressing α4 decreased in TC, but not in SCI, subjects. Likewise, the percentage of neutrophils and monocytes expressing CD11d decreased markedly in TC subjects, but not after SCI. In contrast, the mean surface expression of α4 and CD11d by neutrophils and monocytes increased after SCI compared with uninjured and TC subjects. The percentage of cells and surface expression of CD11b were similar in neutrophils of all three groups, whereas CD11b surface expression increased after SCI in monocytes. In summary, unlike changes found after general trauma, the proinflammatory stimulation induced by SCI increases the surface expression of adhesion molecules on circulating neutrophils and monocytes before they infiltrate the injured spinal cord and multiple organs of patients. Integrins may be excellent targets for anti-inflammatory treatment after human SCI.

The SCIentinel study - prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS) - study protocol and interim feasibility data

“…We defined the eligibility criteria (Table 1 ) in order to minimize inclusion bias and to obtain 'representative’ data. The definitions stipulated in the SCIentinel protocol are consistent with previously published studies [ 6 , 8 , 18 , 30 ]. It was necessary to exclude patients with severe, life threatening polytrauma or severe TBI in order to limit variability caused by concomitant injury.…”

CD11d β2 integrin expression on human NK, B, and γδ T cells

“…CD11d was previously reported to be expressed on the cell surface of a proportion of human lymphocytes [1,16]. While studying the expression of b2 integrins on blood myeloid cells in the context of human spinal cord injury [17], we also observed, but did not report on, a population of CD11dexpressing lymphocytes. Here, in a separate group of healthy and spinal cord-injured human participants, we confirm that a subpopulation of human lymphocytes expresses CD11d.…”

The Systemic Inflammatory Response after Spinal Cord Injury in the Rat Is Decreased by α4β1 Integrin Blockade

“…Accordingly the anti-α4β1 treatment might block a larger portion of the diapedesis process. Next, expression of the two different integrins on human neutrophils and monocytes follows a generally similar time course after SCI, but expression of α4β1 on neutrophils increases sooner than CD11d/CD18 (12 h versus 48 h) (Bao et al, 2011a). Furthermore, binding of α4β1 to a ligand increases its avidity.…”