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[The relationship between complement C3 receptors (CR1, CR3) on polymorphonuclear leukocytes and complement fragments
M Ueda1, M Deguchi, S Takemura
1First Department of Internal Medicine, Kyoto Prefectural University of Medicine.
Insights
Hemodialysis increases complement receptor expression on white blood cells. Complement fragment C5a plays a key role in this immune response during dialysis.
Area of Science:
- Immunology
- Nephrology
- Biochemistry
Background:
- Cuprammonium rayon hemodialysis membranes activate the complement system.
- Polymorphonuclear leukocytes (PMNs) express complement receptors CR1 and CR3.
- Complement activation generates various fragments, including C3a, C5a, C4d, iC3b, and Bb.
Purpose of the Study:
- To investigate the expression of CR1 and CR3 on PMNs during hemodialysis.
- To examine the generation of complement fragments during hemodialysis.
- To determine the relationship between complement fragments and CR1/CR3 expression on PMNs.
Main Methods:
- Analysis of CR1 and CR3 expression on PMNs in hemodialysis patients.
- Measurement of plasma complement fragments (C3a, C5a, C4d, iC3b, Bb) during dialysis.
- In vitro studies using purified complement fragments (Bb, C5a) and PMNs from healthy donors.
- Assessment of nafamostat mesilate's effect on complement receptor expression.
Main Results:
- CR1 and CR3 expression on PMNs significantly increased during hemodialysis.
- Plasma levels of C3a, C5a, and iC3b initially rose and then decreased.
- Plasma Bb levels remained elevated throughout hemodialysis.
- In vitro, C5a augmented CR1 and CR3 expression on PMNs, while Bb had no effect.
- Nafamostat mesilate inhibited C5a-induced augmentation in a dose-dependent manner.
Conclusions:
- Complement activation during hemodialysis leads to increased expression of CR1 and CR3 on PMNs.
- The complement fragment C5a is a key mediator in upregulating CR1 and CR3 expression.
- Understanding these interactions may inform strategies to mitigate complement-mediated inflammatory responses during dialysis.
Abstract:
The expression of complement receptor type 1 (CR1) and type 3 (CR3) on polymorphonuclear leukocytes (PMNs) and generation of complement fragments, C3a, C5a, C4d, iC3b and Bb, were studied in patients during hemodialysis using cuprammonium rayon (Cu) membranes. Furthermore, the relation between the expression of CR1 and CR3 on PMNs from healthy donors and complement fragments was investigated. The expression of CR1 and CR3 on PMNs increased during hemodialysis. Plasma C3a, C5a and iC3b levels increased in the first 15 minutes and then decreased at 120 minutes of dialysis. But plasma Bb level remained high until the end of hemodialysis. Purified Bb had no effect on the expression of CR1 and CR3 on PMNs, but C5a augmented those expression in vitro. Nafamostat mesilate, an artificial proteinase inhibitor, inhibited augmentation of complement receptors on PMNs in concentration dependent fashion. C5a generated through the activation of complement was thought to take an important role in the increased expression of CR1 and CR3 on PMNs.