Background Polymorphonuclear neutrophils (PMNs) with irregular properties have been reported in patients with lupus and compelling evidence implicates them as a source of self-antigens. PMNs are the most abundant circulating leukocytes in human blood; defining their implication either as inherently defective players or as cells affected by external factors (e.g. autoantibodies, immune complexes and type I interferon) is of interest. We propose that elements present in the blood of patients with lupus affect neutrophil function/viability, in a NETosis-independent fashion.
Methods PMNs were isolated from venous blood of healthy volunteers and incubated with serum from normal subjects or from patients with lupus. Apoptosis and necrosis were assessed in real-time by cell surface exposure of phosphatidylserine (PS) and loss of plasma membrane integrity, respectively. Serums’ analytes measurements were made by Luminex and ELISA.
Results Serums from patients with lupus caused a transient increase in PS exposure on the outer leaflet of PMN plasma membrane, in a significantly more intense fashion than serums from normal individuals. This peculiar phenomenon, which does not have characteristics of classic apoptosis, correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), in contrast to any of the following serum analytes: cytokines, chemokines, circulating growth factors, HMGB1, S100A8 and A9 proteins, complement components C3 and C4, immunoglobulins (IgA, IgG, IgM) and leukocyte counts. However, the transient PS increase was abolished by the decomplementation of the serums or by blocking the Fc receptors on PMNs’ surface.
Conclusions Healthy PMNs are affected by the serum of patients with lupus. The transient PS exposure on the outer leaflet of the cellular membrane constitutes a new phenotype directly linked with factors that are at play in the blood of patients. Ongoing studies are looking at the nature of this new phenotype and how it links with PMNs being a potential source of self-antigens and/or as players unduly activated in lupus.
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