Interactions of Platelet Activating Factor and Prostaglandins in the Glomerulus and in Mesangial Cells

1989 ◽  
pp. 199-219 ◽  
Author(s):  
Detlef Schlondorff
Keyword(s):  
Mesangial Cells ◽  
Platelet Activating Factor

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

scholarly journals Angiotensin II causes formation of platelet activating factor in cultured rat mesangial cells.

1989 ◽  
Vol 64 (6) ◽  
pp. 1224-1229 ◽  
Author(s):  
R Neuwirth ◽  
J A Satriano ◽  
S DeCandido ◽  
K Clay ◽  
D Schlondorff
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cells ◽  
Platelet Activating Factor

Vasoconstrictor-evoked prostaglandin synthesis in cultured human mesangial cells

1985 ◽  
Vol 248 (2) ◽  
pp. F240-F246 ◽  
Author(s):  
N. Ardaillou ◽  
J. Hagege ◽  
M. P. Nivez ◽  
R. Ardaillou ◽  
D. Schlondorff
Keyword(s):  
Arginine Vasopressin ◽  
Mesangial Cells ◽  
Platelet Activating Factor ◽  
Feedback Mechanism ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Human Mesangial Cells ◽  
Cell Contractility ◽  
Human Glomerular Mesangial Cells ◽  
Cells Cultured

We examined the influence of angiotensin II (ANG II), arginine vasopressin (AVP), and platelet activating factor (PAF) on prostaglandin (PG) synthesis and cell contractility in human glomerular mesangial cells in culture. Addition of sodium butyrate to the culture medium for 40 h significantly increased synthesis of both 6-keto-PGF1 alpha and PGE2 in the presence of exogenous arachidonic acid and of PGE2 under basal conditions. To optimize conditions in all further experiments, cells cultured with butyrate were studied. Under basal conditions, cultured mesangial cells produced predominantly 6-keto-PGF1 alpha and much less PGE2. Addition of either ANG II, AVP, or PAF all resulted in a rapid (within minutes) two- to threefold stimulation of 6-keto-PGF1 alpha and PGE2. Threshold stimulations were obtained at 10 pM for ANG II, 1 nM for AVP, and 10-100 pM for PAF. Preincubation of the cells with [Sar1,Ala8]ANG II, an antagonist of ANG II, inhibited ANG II-enhanced PG production, and preincubation with 1-desamino-8-D-arginine vasopressin, an antidiuretic analogue, blunted AVP-enhanced PG production. Under phase-contrast microscopy, PAF, ANG II, and, to a lesser degree, AVP caused decrease in cell surface area of mesangial cells cultured without butyrate at concentrations similar to those stimulating PG synthesis. Only PAF contracted cells cultured with butyrate, indicating attenuation of the vasoactive effects of ANG II and AVP when synthesis of PG was increased. However, a lower dose of PAF was only active when PG synthesis was inhibited, suggesting the same feedback mechanism for the three agonists.

Platelet-activating factor stimulates multiple signaling pathways in cultured rat mesangial cells

1992 ◽  
Vol 153 (2) ◽  
pp. 244-255 ◽  
Author(s):  
Mark Kester ◽  
Christie P. Thomas ◽  
Jin Wang ◽  
Michael J. Dunn
Keyword(s):  
Signaling Pathways ◽  
Mesangial Cells ◽  
Platelet Activating Factor ◽  
Multiple Signaling

Production of platelet-activating factor in glomeruli and cultured glomerular mesangial cells

1986 ◽  
Vol 250 (6) ◽  
pp. F1123-F1127 ◽  
Author(s):  
D. Schlondorff ◽  
P. Goldwasser ◽  
R. Neuwirth ◽  
J. A. Satriano ◽  
K. L. Clay
Keyword(s):  
Mesangial Cells ◽  
Platelet Activating Factor ◽  
Gas Chromatography Mass Spectrometry ◽  
Cell Protein ◽  
Rabbit Platelet ◽  
Glomerular Mesangial Cells ◽  
Glomerular Function ◽  
Isolated Glomeruli ◽  
Major Species ◽  
Layer Chromatography

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) results in contraction of isolated glomeruli and cultured mesangial cells and concomitantly causes release of arachidonic acid and prostaglandin E2 (PGE2) formation. The kidney and isolated glomeruli can also generate material that has PAF bioactivity. We therefore examined the capacity of isolated renal glomeruli and cultured glomerular mesangial cells from rats to form PAF. Both isolated glomeruli and cultured mesangial cells transformed 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine ([3H]lyso-PAF) into a labeled product comigrating both on thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) with authentic PAF. Using rabbit platelet aggregation as bioassay for PAF, we found that isolated glomeruli produced 4 +/- 2 pmol/mg glomerular protein of PAF-like material, and mesangial cells produced 30 +/- 8 pmol/mg cell protein when stimulated with A23187 (10(-5) M) for 30 min. The major species of the PAF material produced by mesangial cells was identified as 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine after HPLC separation, followed by fast atom bombardment and gas chromatography-mass spectrometry. These results show that glomerular mesangial cells can produce PAF, which could contribute locally to the regulation of glomerular function.

Glomerular endothelial cells respond to calcium-mobilizing agonists with release of EDRF

1990 ◽  
Vol 258 (5) ◽  
pp. F1295-F1303 ◽  
Author(s):  
P. A. Marsden ◽  
T. A. Brock ◽  
B. J. Ballermann
Keyword(s):  
Endothelial Cells ◽  
Calcium Concentration ◽  
Mesangial Cells ◽  
Platelet Activating Factor ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Concentration Dependent Manner ◽  
Glomerular Function ◽  
Glomerular Endothelial Cells

To determine whether glomerular endothelial cells (GEN) may play a role in the local control of glomerular function by releasing endothelium-derived relaxing factor (EDRF), the effect of several agonists on GEN cytosolic calcium concentration ([Ca2+]i) and GEN EDRF release was determined. Bradykinin, ATP, thrombin, and platelet-activating factor (PAF) all increased [Ca2+]i in GEN in a concentration-dependent manner, whereas serotonin, acetylcholine, phenylephrine, and endothelin-1 were without effect. Coincubation of glomerular mesangial cells (GMC) with GEN augmented mesangial cell guanosine 3',5'-cyclic monophosphate (cGMP) content five- to sixfold, Bradykinin elicited a further concentration-dependent increase in GMC cGMP content in the presence but not absence of GEN. The GEN-dependent bradykinin-stimulated GMC cGMP accumulation was abolished by hemoglobin and methylene blue, blunted by gossypol, and augmented by superoxide dismutase. Other agonists capable of augmenting GEN [Ca2+]i also stimulated GMC cGMP accumulation in the presence but not in the absence of GEN. Thus cultured GEN release a factor that stimulates cGMP accumulation in adjacent mesangial cells which has the pharmacological characteristics of EDRF.

scholarly journals Interleukin-12 Is Synthesized by Mesangial Cells and Stimulates Platelet-Activating Factor Synthesis, Cytoskeletal Reorganization, and Cell Shape Change

1999 ◽  
Vol 154 (2) ◽  
pp. 623-632 ◽  
Author(s):  
Benedetta Bussolati ◽  
Filippo Mariano ◽  
Luigi Biancone ◽  
Robert Foà ◽  
Salvatore David ◽  
...  
Keyword(s):  
Cell Shape ◽  
Mesangial Cells ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Interleukin 12 ◽  
Cytoskeletal Reorganization ◽  
Cell Shape Change
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