Megakaryocytic cells synthesize and platelets secrete alpha5-laminins, and the endothelial laminin isoform laminin 10 (alpha5beta1gamma1) strongly promotes adhesion but not activation of platelets.
Following vascular injury, basement membrane (BM) components of the blood vessels are exposed to circulating cells and may contribute to hemostasis and/or thrombosis. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major laminin isoforms of the endothelial BM, and LN-8 is also secreted by activated platelets. In the present study, we demonstrate synthesis of alpha5-laminins LN-10 and LN-11 (alpha5beta2gamma1) by megakaryocytic cells, and intracellular expression of these laminin isoforms in blood platelets. In contrast to platelet LN alpha4 chain that had an apparent molecular weight of 180 kDa and associated mostly to LNbeta1 chain, platelet LNalpha5 consisted of 300/350 kDa polypeptides and associated mainly to LNbeta2. Both alpha4- and alpha5-laminins were secreted by platelets following stimulation. When compared to recombinant human (rh) LN-8, rhLN-10 was much more adhesive to platelets, though adhesion to both proteins was largely mediated via alpha6beta1 integrin. In spite of their adhesive properties, rhLN-8 and rhLN-10 induced neither P-selectin expression nor cell aggregation, two signs of platelet activation. This study demonstrates synthesis/expression of heterotrimeric alpha5-laminins in hematopoietic/blood cells, and provides evidence for the adhesive, but not activating, role of endothelial laminin isoforms in platelet biology.
Nigatu
Ayele
A
Department of Odontology, Karolinska Institutet, SE-141 04 Stockholm, Sweden.
Sime
Wondossen
W
Gorfu
Gezahegn
G
Geberhiwot
Tarekegn
T
Andurén
Ingegerd
I
Ingerpuu
Sulev
S
Doi
Masayuki
M
Tryggvason
Karl
K
Hjemdahl
Paul
P
Patarroyo
Manuel
M
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008533:Megakaryocytes / Q000378:metabolism*; D008970:Molecular Weight; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D007797:Laminin; D011994:Recombinant Proteins; C119013:laminin 10; C474559:laminin 11 protein, human; C110308:laminin 8