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Release of arachidonic acid by complement C5b-9 complex in glomerular epithelial cells
1Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
The American Journal of Physiology
|September 1, 1991
Summary
Complement component 5b-9 (C5b-9) activates phospholipase A2 (PLA2) in glomerular epithelial cells (GEC). This activation, mediated by protein kinase C and elevated calcium, increases arachidonic acid release, potentially causing kidney injury.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Membranous nephropathy involves glomerular epithelial cell (GEC) injury and proteinuria.
- Complement component C5b-9 contributes to GEC injury and proteinuria.
- Arachidonic acid metabolites play a role in C5b-9-induced GEC injury.
Purpose of the Study:
- To investigate the mechanisms by which C5b-9 stimulates arachidonic acid production in GEC.
- To determine the role of protein kinase C (PKC) and calcium in C5b-9-mediated arachidonic acid release.
Main Methods:
- Cultured GEC were labeled with [3H]arachidonate.
- GEC were treated with C5b-9, and levels of free arachidonic acid and diacylglycerol (DAG) were measured.
- PKC activity was assessed in GEC depleted of PKC using phorbol myristate acetate.
- Phospholipase A2 (PLA2) activity was measured in GEC homogenates.
Main Results:
- C5b-9 increased free arachidonic acid and DAG in GEC.
- PKC depletion significantly inhibited C5b-9-induced arachidonate release.
- C5b-9 directly increased PLA2 activity in GEC.
- PLA2 activation was linked to PKC activation and elevated intracellular calcium ([Ca2+]i).
Conclusions:
- C5b-9 activates PLA2 in GEC, leading to increased arachidonic acid release.
- This activation is dependent on PKC and elevated [Ca2+]i.
- C5b-9-induced PLA2 activation may contribute to glomerular injury and proteinuria in membranous nephropathy.