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Endothelial cell destruction by polymorphonuclear leukocytes incubated with sera from patients with systemic lupus
Y Hashimoto1, K Nakano, S Yoshinoya
1Department of Internal Medicine & Physical Therapy, University of Tokyo School of Medicine, Japan.
Abstract:
When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti-EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease.
Insights
Normal white blood cells showed increased toxicity against blood vessel cells when exposed to sera from patients with active systemic lupus erythematosus (SLE). Immune complexes in SLE sera likely drive this vascular damage.
Area of Science:
- Immunology
- Pathology
- Vascular Biology
Background:
- Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation and potential organ damage.
- Vascular endothelial cells (EC) play a crucial role in maintaining blood vessel integrity and regulating inflammation.
Purpose of the Study:
- To investigate the cytotoxic effects of sera from active SLE patients on human vascular endothelial cells (EC).
- To identify the factors within SLE sera responsible for inducing this cytotoxicity.
Main Methods:
- Incubation of normal polymorphonuclear leukocytes (PMN) with sera from SLE patients and healthy controls.
- Assessment of EC cytotoxicity using the standard 51Cr release assay.
- Immune complex quantification and absorption studies using C1q-Sepharose 4B.
- Gel fractionation to analyze the heterogeneity of cytotoxic factors.
Main Results:
- Sera from active SLE patients induced significantly higher cytotoxicity against EC compared to normal sera.
- The level of cytotoxicity correlated with immune complex levels in SLE sera.
- Cytotoxicity did not correlate with the presence of anti-EC antibodies.
- Absorption studies confirmed the role of immune complexes in inducing cytotoxicity.
- Gel fractionation revealed heterogeneity, suggesting potential contributions from other factors like anti-EC antibodies in some cases.
Conclusions:
- Immune complexes in SLE sera are a primary factor inducing cytotoxicity against vascular endothelial cells.
- This immune complex-mediated cytotoxicity may contribute to vascular inflammation and damage in SLE.
- Further investigation is needed to fully elucidate the heterogeneous nature of cytotoxic factors in SLE.