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Direct interactions between platelets and cultured rat mesangial cells
I Arribas1, R Martín Ambrosio, M L Díez Marqués
1Clinical Chemistry Department, Hospital Príncipe de Asturias, Madrid, Spain.
Abstract:
Platelets seem to be involved in the pathogenesis of some kidney diseases, but the exact relationships between platelets and the changes in renal function are incompletely known. Mesangial cells (MC) were incubated with platelet-supernatants (PS) and cellular surface area (CSA) and myosin light-chain phosphorylation (MLCP) were measured. CSA of PS-incubated MC (PS-MC) significantly diminished, as compared to control MC (70 +/- 6% vs. 100 +/- 5%). PS induced a significant increase in MLCP with respect to control cells (150 +/- 23% vs. 100 +/- 18%). When platelets were pretreated with indomethacin, the PS-dependent contraction was abolished. Pretreatment with sulotroban (SU) or BN-52021 (BN), a thromboxane A2 (TXA2) and a platelet-activating factor (PAF) receptor blocker respectively, also completely blocked the PS effects. In other experiments, platelets were activated with thrombin (T), adding the so obtained PS to MC. Moreover, cells were also preincubated with T and then added PS. No changes in CSA were observed in either case. It may be concluded that PS contracted cultured MC, and these changes could be related to the decreased glomerular filtration rate (GFR) observed in some diseases in which platelets seem to be involved. TXA2 and PAF may be responsible for this effect. In contrast, T incubation inhibited the effect of PS, perhaps through a direct relaxing effect of T in MC.
Insights
Platelet supernatants contract mesangial cells, potentially reducing kidney function. Thromboxane A2 and platelet-activating factor mediate this effect, highlighting their role in kidney disease pathogenesis.
Area of Science:
- Nephrology
- Hematology
- Cell Biology
Background:
- Platelets are implicated in kidney disease pathogenesis, but their precise role in renal function changes remains unclear.
- Understanding platelet interactions with kidney cells is crucial for deciphering disease mechanisms.
Purpose of the Study:
- To investigate the effect of platelet-derived factors on mesangial cells (MC).
- To identify specific platelet mediators responsible for observed cellular changes and their potential link to reduced glomerular filtration rate (GFR).
Main Methods:
- Mesangial cells were incubated with platelet supernatants (PS).
- Cellular surface area (CSA) and myosin light-chain phosphorylation (MLCP) were measured.
- Platelets were pretreated with indomethacin, thromboxane A2 (TXA2) receptor blocker (sulotroban), or platelet-activating factor (PAF) receptor blocker (BN-52021) to assess mediator roles.
Main Results:
- Platelet supernatants significantly reduced MC surface area and increased MLCP.
- Pretreatment of platelets with indomethacin, sulotroban, or BN-52021 abolished these effects.
- Thrombin activation of platelets inhibited the PS-induced contraction of MC.
Conclusions:
- Platelet supernatants induce mesangial cell contraction, potentially contributing to decreased GFR in certain kidney diseases.
- Thromboxane A2 and platelet-activating factor are key mediators of this platelet-induced mesangial cell response.
- Thrombin may exert a protective effect by inhibiting platelet-induced mesangial cell contraction.