Differential Involvement of ERK2 and p38 in platelet adhesion to collagen.
We investigated the role of two MAP kinases, ERK2 and p38, in platelet adhesion and spreading over collagen matrix in static and blood flow conditions. P38 was involved in collagen-induced platelet adhesion and spreading in static adhesion conditions, whereas ERK2 was not. In blood flow conditions, with shear rates of 300 or 1500 s(-1), ERK2 and p38 displayed differential involvement in platelet adhesion, depending on the presence or absence of the von Willebrand factor (vWF). Low collagen coverage densities (0.04 microg/cm2) did not support vWF binding. During perfusions over this surface, platelet adhesion was not affected by the inhibition of ERK2 phosphorylation by PD 98059. However, abolishing p38 activation by SB 203580 treatment reduced platelet adhesion by 67 +/- 9% at 300 s(-1) and 56 +/- 2% at 1500 s(-1). In these conditions, the p38 activity required for platelet adhesion depends on the alpha2beta1 collagen receptor. At higher collagen coverage densities (0.8 microg/cm2) supporting vWF binding, the inhibition of ERK2 activity by PD 98059 decreased adhesion by 47 +/- 6% at 300 s(-1) and 72 +/- 3% at 1500 s(-1), whereas p38 inhibition had only a small effect. The ERK2 activity required for platelet adhesion was dependent on the interaction of vWF with GPIb. In conclusion, ERK2 and p38 have complementary effects in the control of platelet adhesion to collagen in a shear stress-dependent manner.
Mazharian
Alexandra
A
Hôpital Lariboisière, U689 INSERM, IFR139, 8 rue Guy Patin, Paris 75010, France.
Roger
Séverine
S
Maurice
Pascal
P
Berrou
Eliane
E
Popoff
Michel R
MR
Hoylaerts
Marc F
MF
Fauvel-Lafeve
Françoise
F
Bonnefoy
Arnaud
A
Bryckaert
Marijke
M
D000199:Actins / Q000737:chemistry; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D038982:Integrin alpha2beta1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D014841:von Willebrand Factor / Q000378:metabolism
D000199:Actins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D038982:Integrin alpha2beta1; D019038:Platelet Glycoprotein GPIb-IX Complex; D011725:Pyridines; D014841:von Willebrand Factor; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one