Selective CD11a upregulation on neutrophils in the acute phase of steroid-responsive meningitis-arteritis in dogs

Abstract

Steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease of juvenile to young adult dogs with a relapsing course and most prominent manifestation in the cervical meninges. The most important laboratory finding is a marked neutrophilic pleocytosis. Integrin (CD11a, b, c) expression on polymorphonuclear cells (PMNs) was quantified by immunophenotyping and subsequent flow cytometric measurements. Values were determined for peripheral blood in the acute phase of SRMA ( n = 14) as well as during glucocorticosteroid treatment ( n = 16). Results were compared to those from dogs with other neurological diseases ( n = 49) and healthy individuals ( n = 7). Integrin expression was also investigated on PMNs deriving from cerebrospinal fluid (CSF) of dogs in the acute phase of SRMA ( n = 14). In a second part of the study PMNs of healthy dogs were incubated with sera of dogs in the acute phase of SRMA ( n = 12). The influence on integrin expression was studied and results were compared to those after incubation with pooled sera of dogs suffering from idiopathic epilepsy ( n = 3). PMNs in peripheral blood of dogs in the acute phase of SRMA showed higher values of CD11a expression when compared to dogs under treatment and to control groups, whereas CD11b and c expression was comparable among the different groups. In the acute phase of SRMA CD11b expression on PMNs in CSF was increased in comparison to that in peripheral blood. Incubation with SRMA sera caused a stronger upregulation of CD11a than did pooled epilepsy sera in 9/12 cases whereas an upregulation of CD11b and c was observed in single cases only. High CD11a expression on PMNs in peripheral blood appears to be an important factor in the pathogenesis of SRMA. This integrin is known to be essential for adhesion of PMNs within the neutrophil recruitment cascade and therefore might mediate the enhanced invasion of neutrophils into the subarachnoidal space eventually leading to meningitis and clinical signs. Since sera of dogs suffering from SRMA selectively induce an upregulation of CD11a it can be suspected that this fluid contains one or multiple factors being responsible for this.