Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and felty's syndrome sera

Abstract

The ability of sera from patients with systemic lupus erythematosus (SLE) and Felty's syndrome to induce increased adhesiveness of normal human neutrophils (PMN) was investigated. PMN from normal healthy donors were incubated in sera from 19 patients with active SLE, 12 with inactive SLE, 20 with Felty's, 24 with rheumatoid arthritis, and 34 normal persons. After incubation, the degree of adherence of the PMN to human endothelial cells in culture, their aggregation, and superoxide (O2‐) generation were determined. Sera from patients with both active SLE and Felty's syndrome induced significantly increased PMN adherence to endothelial cells and PMN aggregation in vitro, compared with normal sera. This increased adherence to endothelial cells was maintained after heat treatment (56°C for 30 minutes) of the sera. In O2‐ generation experiments, sera from patients with active SLE induced significantly increased O2‐ release from normal PMN using both fresh and heat‐treated sera. Sera from Felty's patients demonstrated the same effect with heattreated sera but not with fresh sera. When sera from patients with active SLE and Felty's syndrome were used, all three parameters correlated significantly with each other in individual patients. In contrast, sera from the 12 patients with inactive SLE and 24 rheumatoid arthritis patients without Felty's failed to induce significant differences in the three parameters studied when compared with 34 normal controls. Fractionation of 3 SLE sera and 1 Felty's serum on Sephadex G‐200 demonstrated that the adherence enhancing factor was present in both IgG and IgG‐excluded fractions. The observed increased adhesiveness of PMN induced by SLE and Felty's sera may, at least in part, contribute to the neutropenia which is common in these diseases. Increased O2‐ release associated with PMN adherence may contribute to endothelial cell damage and vascular injury, which is also a common manifestation of these diseases.

The leukergy test in rheumatic diseases. New implications for an old test

“…Hashimoto and associates (7) recently found increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in sera from patients with SLE and Felty's syndrome. The increased superoxide release associated with PMN adherence is a possible etiologic factor in the development of endothelial damage.…”

Neutropenia in patients receiving anti–tumor necrosis factor therapy

“…In contrast to the relatively benign chronic autoimmune neutropenia, drug-induced neutropenia, or agranulocytosis, is an idiosyncratic reaction that has a high rate of infectious complications and a mortality rate of approximately 10% (19,20). The most common drugs associated with this include antithyroid medications and sulfonamides.…”

Evaluation of disease activity in rheumatic patients by leucocyte adhesiveness/aggregation.

“…Increased adherence to the endothelium might be harmful to these cells'6 and this may play a part in the development of inflammation in various rheumatic diseases. [17][18][19][20][21] In summary, the state of leucocyte adhesiveness/ aggregation is a simple, convenient, and reliable test for assessing the severity of disease in patients with various rheumatic diseases. In addition to its potential clinical usefulness, this variable also contributes to our understanding of the role of leucocytes in inflammation.…”