Megakaryocytic cells synthesize and platelets secrete α5-laminins, and the endothelial laminin isoform laminin 10 (α5β1γ1) strongly promotes adhesion but not activation of platelets

Ayele Nigatu; Wondossen Sime; Gezahegn Gorfu; Tarekegn Geberhiwot; Ingegerd Andurén; Sulev Ingerpuu; Masayuki Doi; Karl Tryggvason; Paul Hjemdahl; Manuel Patarroyo

doi:10.1160/TH05-04-0281

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 85-93
DOI: 10.1160/TH05-04-0281

Platelets and Blood Cells

Schattauer GmbH

Megakaryocytic cells synthesize and platelets secrete α5-laminins, and the endothelial laminin isoform laminin 10 (α5β1γ1) strongly promotes adhesion but not activation of platelets

Authors

Ayele Nigatu

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden
Wondossen Sime

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden
Gezahegn Gorfu

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden
Tarekegn Geberhiwot

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden
Ingegerd Andurén

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden
Sulev Ingerpuu

²Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
Masayuki Doi

³Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Karl Tryggvason

³Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Paul Hjemdahl

⁴Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), Stockholm, Sweden
Manuel Patarroyo

¹Department of Odontology, and Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden

Abstract

Summary

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) (α4β1γ1) and 10 (LN-10) (α5β1γ1) 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 α5-laminins LN-10 and LN-11 (α5β2γ1) by megakaryocytic cells, and intracellular expression of these laminin isoforms in blood platelets. In contrast to platelet LNα4 chain that had an apparent molecular weight of 180 kDa and associated mostly to LNβ1 chain, platelet LNα5 consisted of 300/350 kDa polypeptides and associated mainly to LNβ2. Both α4– and α5-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 α6β1 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 α5-laminins in hematopoietic/blood cells, and provides evidence for the adhesive, but not activating, role of endothelial laminin isoforms in platelet biology.

Keywords

Endothelial laminins - platelet adhesion/activation - integrins

Full Text

References

References
1 Kalluri R. Basement membranes: Structure, assembly and role in tumour angiogenesis. Nature Rev 2003; 03: 422-33.
2 Wondimu Z, Geberhiwot T, Ingerpuu S. et al. An endothelial laminin isoform, laminin 8 (α4β1γ1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis. Blood 2004; 104: 1859-66.
3 Andrews RK, Berndt MC. Platelet physiology and thrombosis. Thromb Res 2004; 114: 447-453.
4 Rendu F, Brohard-Bohn B. The platelet release reaction: granules’ constituents, secretion and functions. Platelets 2001; 12: 261-73.
5 Ekblom P, Timpl R. The laminins. Harwood Academic Publishers; Amsterdam: 1996
6 Patarroyo M, Tryggvason K, Virtanen I. Laminin isoforms in tumor invasion, angiogenesis and metastasis. Sem. Cancer Biol 2002; 12: 197-207.
7 Miner JH, Yurchenco PD. Laminin functions in tissue morphogenesis. Ann Rev Cell Dev Biol 2004; 20: 255-84.
8 Aumailley M, Bruckner-Tuderman L, Carter WG. et al. A simplified laminin nomenclature. Matrix Biol 2005; 24: 326-32.
9 Miner JF, Patton BL, Lentz SI. et al. The laminin α chains: Expression, developmental transitions, and chromosomal localization of α1-α5, identification of heterotrimeric laminins 8–11, and cloning of a novel α3 isoform. J Cell Biol 1997; 137: 685-701.
10 Frieser M, Nöckel H, Pausch F. et al. Cloning of mouse laminin α4 cDNA. Expression in a subset of endothelium. Eur J Biochem 1997; 246: 727-35.
11 Petäjäniemi N, Korhonen M, Kortesmaa J. et al. Localization of laminin α4 chain in developing and adult human tissues. J Histochem Cytochem 2002; 50: 1113-30.
12 Sorokin LM, Pausch F, Frieser M. et al. Developmental regulation of the laminin α5 chain suggestsa role in epithelial and endothelial cell maturation. Dev Biol 1997; 189: 285-300.
13 Geberhiwot T, Ingerpuu S, Pedraza C. et al. Blood platelets contain and secrete laminin-8 (α4β1γ1) and adhere to laminin-8 via α6β1 integrin. Exp Cell Res 1999; 253: 723-32.
14 Kikkawa Y, Sanzen N, Fujiwara H. et al. Integrin binding specificity of laminin-10/11: Laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. J Cell Sci 2000; 113: 869-76.
15 Kortesmaa J, Yurchenco P, Tryggvason K. Recombinant laminin-8 (α4β1γ1). Production, purification and interaction with integrins. J Biol Chem 2000; 275: 14583-9.
16 Nishiuchi R, Murayama O, Fujiwara H. et al. Characterization of the ligand-binding specificities of integrin alpha3beta1 and alpha6beta1 using a panel of purified laminin isoforms containing distinct alpha chains. J Biochem 2003; 134: 497-504.
17 Tryggvason K, Oikarinen J, Viinikka L. et al. Effects of laminin, proteoglycan and type IV collagen, components of basement membranes, on platelet aggregation. Biochem Biophys Res Com 1981; 100: 233-9.
18 Ill CR, Engvall E, Ruoslahti E. Adhesion of platelets to laminin in the absence of activation. J Cell Biol 1984; 99: 2140-5.
19 Sonnenberg A, Modderman PW, Hogervorst F. Laminin receptor on platelets is the integrin receptor VLA-6. Nature 1988; 336: 487-9.
20 Virtanen I, Gullberg D, Rissanen J. et al. Laminin α1-chain shows a restricted distribution in epithelial basement membranes of fetal and adult human tissues. Exp Cell Res 2000; 257: 298-309.
21 Doi M, Thyboll J, Kortesmaa J. et al. Recombinant human laminin-10 (α5β1γ1). Production, purification, and migration-promoting activity on vascular endothelial cells. J Biol Chem 2002; 277: 12741-8.
22 Kortesmaa J, Doi M, Patarroyo M. et al. Chondroitin sulphate modification in the α4 chain of human recombinant laminin-8 (α4β1γ1). Matrix Biol 2002; 21: 483-6.
23 Engvall E, Davis GE, Dickerson K. et al. Mapping of domains in human laminin using monoclonal antibodies: Localization of the neurite-promoting site. J Cell Biol 1986; 103: 2457-65.
24 Tiger CF, Champliaud MF, Pedrosa-Domellof F. et al. Presence of laminin alpha 5 chain and lack of laminin alpha 1 chain during human muscle development and in muscular dystrophies. J Biol Chem 1997; 272: 28590-5.
25 Kikkawa Y, Sanzen N, Sekiguchi K. Isolation and characterization of laminin-10/11 secreted by human lung carcinoma cells. J Biol Chem 1998; 273: 15854-9.
26 Geberhiwot T, Ingerpuu S, Pedraza C. et al. Erythromegakaryocytic cells synthesize laminin-8 (α4β1γ1). Exp Cell Res 2000; 254: 189-95.
27 Martin P, Papayannopoulou T. HEL cells: A new human erythroleukemia cell line with spontaneous and induced globin expression. Science 1982; 216: 1233-5.
28 Greenberg SM, Rosenthal DS, Greenley TA. et al. Characterization of a new megakaryocytic cell line: The DAMI cell. Blood 1988; 72: 1968-77.
29 Geberhiwot T, Wondimu Z, Salo S. et al. Chain specificity assignment of monoclonal antibodies to human laminins by using recombinant laminin β1 and γ1 chains. Matrix Biol 2000; 19: 163-7.
30 Engvall E, Earwicker D, Haaparanta T. et al. Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regul 1990; 01: 731-40.
31 Urieli-Shoval A, Shubinsky G, Linke RP. et al. Adhesion of human platelets to serum amyloid A. Blood 2002; 99: 1224-9.
32 Hjemdahl P, Chronos NA, Wison DJ. et al. Epinephrine sensitizes human platelets in vitro and in vivo as studied by fibrinogen binding and P-selectin expression. Atheroscler Thromb 1994; 14: 77-84.
33 Wallen NH, Held C, Rehnqvist N. et al. Impact of treatment with acetylsalicylic acid on the proaggregatory effects of adrenaline in vitro in patients with stable angina pectoris: influence of the anticoagulant. Clin Sci 1993; 85: 577-83.
34 Vogel W, Kanz L, Brugger W. et al. Expression of laminin β2 chain in normal human bone marrow. Blood 1999; 94: 1143-5.
35 Shattil SJ, Newman PJ. Integrins: dynamic scaffolds for adhesion and signaling in platelets. Blood 2004; 104: 1606-15.
36 Miner JH, Lewis RM, Sanes JR. Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues. J Biol Chem 1995; 270: 28523-6.
37 Miner JH, Cunningham J, Sanes JR. Roles for laminin in embryogenesis, exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha 5 chain. J Cell Biol 1998; 143: 1713-23.
38 Thyboll J, Kortesmaa J, Cao R. et al. Deletion of laminin α4 chain leads to impaired microvessel maturation. Mol Cell Biol 2002; 22: 1194-202.
39 Gu Y, Sorokin LM, Durbeej M. et al. Characterization of bone marrow laminins and identification of α5-containing laminins as adhesive proteins for multipotent hematopoietic FDCP-mix cells. Blood 1999; 93: 2533-42.
40 Gu Y, Kortesmaa J, Tryggvason K. et al. Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells. Blood 2003; 101: 877-85.
41 Spessotto P, Gronkowska A, Deutzmann R. et al. Preferential locomotion of leukemic cells towards laminin isoforms 8 and 10. Matrix Biol 2003; 22: 351-61.
42 Risteli J, Rohde H, Timpl R. Sensitive radioimmunoassay for 7 S collagen and laminin: Applications to serum and tissue studies of basement membranes. Anal Biochem 1981; 113: 372-8.
43 Siler U, Seiffert M, Puch S. et al. Characterization and functional analysis of laminin isoforms in human bone marrow. Blood 2000; 98: 4194-203.
44 Handagama P, Rappolee DA, Werb Z. et al. Platelet α-granule fibrinogen, albumin and immunoglobulin G are not synthesized by rat and mouse megakaryocytes. J Clin Invest 1990; 86: 1364-8.
45 Ferletta M, Ekblom P. Identification of laminin-10/11 as a strong cell adhesive complex for a normal and a malignant epithelial cell line. J Cell Sci 1999; 112: 1-10.
46 Yu H, Talts JF. Beta1 integrin and alpha-distroglycan binding sites are localized to different laminin G-domain-like (LG) modules within the laminin alpha 5 chain G domain. Biochem J 2003; 371: 289-99.
47 Farndale RW, Sixma JJ, Barnes MJ. et al. The role of collagen in thrombosis and hemostasis. J Thromb Haemost 2004; 02: 561-73.
48 Willette RN, Storer BL, Clark RK. et al. Human laminin produces human platelet aggregation in vitro . Life Sci 1994; 55: 379-88.
49 Hindriks G, Ijsseldijk MJ, Sonnenberg A. et al. Platelet adhesion to laminin: role of Ca²⁺ and Mg²⁺ ions, shear rate and platelet membrane glycoproteins. Blood 1992; 79: 928-35.
50 Buchanan MR, Richardson M, Haas TA. et al. The basement membrane underlying the vascular endothelium is not thrombogenic: in vitro and in vivo studies with rabbit and human tissues. Thromb Haemost 1987; 58: 698-704.