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Prednisolone interferes with neutrophil adhesion and neutrophil mediated endothelial injury
1Department of Rheumatology, The Karolinska Institute at Huddinge University Hospital, Sweden.
Abstract:
Adhesion of leukocytes to vascular endothelium is a crucial step in inflammation. This interaction may result in damage of the endothelial cells (EC). We evaluated the effects of prednisolone on adhesive interactions between human polymorphonuclear neutrophil granulocytes (PMN) and human umbilical vein endothelial cells (HUVEC) as well as PMN mediated cytotoxicity to HUVEC (as release of 51chromium), mediated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipoxin A4 (LXA4), and the calcium ionophore A23187 in vitro. Prednisolone dose-dependently interfered with adhesion and cytotoxicity induced by fMLP. Prednisolone (at 10 microM) led to a 39% reduction of adhesion and an almost complete inhibition of cytotoxicity, mainly by effects on the PMN. Prednisolone also interfered with cytotoxicity induced by LXA4 by effects on PMN as well as on HUVEC. Adhesion and cytotoxicity induced by the calcium ionophore A23187 was not affected in any way by prednisolone. Thus, in these in vitro models of vasculitis, prednisolone interferes with adhesive and cytotoxic interactions induced by receptor-dependent agonists. These protective effects of prednisolone might explain some of the beneficial effects of glucocorticoids in the treatment of vasculitis.
Insights
Prednisolone reduces leukocyte adhesion and cytotoxicity in models of inflammation, particularly when induced by receptor-dependent agonists. These findings suggest a mechanism for glucocorticoids
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Leukocyte adhesion to vascular endothelium is a key inflammatory process.
- Endothelial cell damage can result from leukocyte interactions.
- Glucocorticoids like prednisolone are used to treat inflammatory conditions such as vasculitis.
Purpose of the Study:
- To investigate the in vitro effects of prednisolone on leukocyte-endothelial cell adhesion.
- To evaluate prednisolone's impact on polymorphonuclear neutrophil (PMN)-mediated cytotoxicity to human umbilical vein endothelial cells (HUVEC).
- To determine if prednisolone affects adhesion and cytotoxicity induced by specific agonists: N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipoxin A4 (LXA4), and calcium ionophore A23187.
Main Methods:
- In vitro assessment of adhesion between human PMN and HUVEC.
- Measurement of PMN-mediated cytotoxicity to HUVEC using 51chromium release assay.
- Exposure to fMLP, LXA4, or A23187 to induce adhesion and cytotoxicity, with and without prednisolone treatment.
Main Results:
- Prednisolone significantly reduced fMLP-induced adhesion and cytotoxicity in a dose-dependent manner, primarily by affecting PMN.
- Prednisolone inhibited LXA4-induced cytotoxicity through actions on both PMN and HUVEC.
- Prednisolone did not affect adhesion or cytotoxicity induced by the calcium ionophore A23187.
Conclusions:
- Prednisolone interferes with receptor-dependent adhesive and cytotoxic interactions between leukocytes and endothelial cells in vitro.
- These anti-adhesive and anti-cytotoxic effects of prednisolone may contribute to its therapeutic benefits in vasculitis.
- The drug's mechanism involves modulating PMN function and, in some cases, endothelial cell responses.