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Lipoxygenase products mediate the attachment of rat macrophages to glomeruli in vitro
Abstract:
Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, we have studied the binding of [3H]-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective. Glomeruli interacted with macrophages in converting arachidonic acid (C20:4) to prostaglandins (PG) since productions of 6 keto-PGF1 alpha, TXB2, and PGD2 by glomeruli and macrophages incubated in combination were much greater than the sums of their respective productions by glomeruli and macrophages incubated separately. Macrophages were the source of the supplementary synthesis of PG which was abolished when these cells were pretreated with aspirin. Stimulation of macrophages by glomeruli was blunted by pretreatment of glomeruli with NDGA. Production of PG and of 12-HETE by macrophages was stimulated by a lipid extract of glomeruli containing the oxygenated metabolites of C20:4. Direct addition of 12-HPETE also stimulated macrophage functions. These data suggest that macrophage attachment to glomeruli and macrophage stimulation in the presence of glomeruli depend on glomerular lipoxygenase activity.
Insights
Macrophage binding to glomeruli in glomerulonephritis is mediated by glomerular lipoxygenase activity. This activity also stimulates macrophages, influencing their interaction with kidney structures.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Macrophages accumulate in Bowman's space during glomerulonephritis.
- Understanding macrophage-glomeruli interactions is crucial for disease mechanisms.
Purpose of the Study:
- To investigate the binding of macrophages to isolated glomeruli.
- To elucidate the role of glomerular enzymatic activity in macrophage adherence and activation.
Main Methods:
- Incubation of [3H]-uridine labeled macrophages with isolated rat glomeruli.
- Assessing binding kinetics and dependence on various factors (protein concentration, temperature, time).
- Investigating the role of glomerular lipoxygenase and cyclooxygenase using specific inhibitors (NDGA, indomethacin) and measuring prostaglandin (PG) and 12-HETE production.
Main Results:
- Macrophage binding to glomeruli is a saturable process influenced by protein concentration, temperature, and time.
- Glomerular lipoxygenase activity, but not cyclooxygenase activity, is essential for macrophage adherence.
- Glomeruli and macrophages synergistically produce prostaglandins (PGs) from arachidonic acid, with macrophages being the source of supplementary PG synthesis.
- Glomerular lipoxygenase metabolites stimulate macrophage production of PGs and 12-HETE.
Conclusions:
- Macrophage attachment to glomeruli is dependent on glomerular lipoxygenase activity.
- Glomerular lipoxygenase activity plays a key role in stimulating macrophages during glomerulonephritis.