Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation.

Laminins are a growing family of large heterotrimeric proteins with cell adhesive and signalling functions. They are major components of basement membranes and are found in many organs, including the vasculature and other compartments of bone marrow, thymus, lymph nodes and spleen. However, expression, recognition and use of laminin isoforms by lymphoid cells are poorly understood. In the present study, lymphoid T cells (Jurkat) were found to synthesize laminin alpha4, beta1 and gamma1 mRNAs and polypeptides and to assemble the chains into laminin-8. Lymphoblastoid B (NAD-20) cells, lymphoid NK (NKL) cells and blood lymphocytes also contained laminin-8 and, after cell permeabilization, practically all blood lymphocytes reacted with mAbs to laminin beta1 and gamma1 chains. Following stimulation, blood lymphocytes secreted laminin-8, and this laminin isoform, but not laminin-10/11(alpha5beta1gamma1/alpha5beta2gamma1), promoted chemokine-induced migration of the cells. In an activation-dependent manner, purified blood CD4 T cells adhered to immobilized laminin-8 and laminin-10/11 by using alpha6beta1 integrin, but minimally to laminin-1 (alpha1beta1gamma1). Accordingly, laminin-8 and laminin-10/11, but not laminin-1, strongly costimulated proliferation of the T cells via the same integrin. Thus, lymphoid cells are able to synthesize and secrete complete laminin molecules. In addition, synthesis of laminin-8 and recognition of laminin-8 and -10/11 by lymphocytes indicate relevance of these laminin isoforms in lymphocyte physiology.

[1]  K. Tryggvason,et al.  Monocytic Cells Synthesize, Adhere to, and Migrate on Laminin-8 (α4β1γ1)1 , 2000, The Journal of Immunology.

[2]  R. Schwartz,et al.  Epithelial Cell-Specific Laminin 5 Is Required for Survival of Early Thymocytes1 , 2000, The Journal of Immunology.

[3]  T. Kiviluoto,et al.  Laminin alpha1-chain shows a restricted distribution in epithelial basement membranes of fetal and adult human tissues. , 2000, Experimental cell research.

[4]  P. Yurchenco,et al.  Form and function: The laminin family of heterotrimers , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[5]  D. McLeod,et al.  Localization of pN-type IIA procollagen on adult bovine vitreous collagen fibrils. , 2000, Matrix biology : journal of the International Society for Matrix Biology.

[6]  K. Tsujikawa,et al.  Interaction of merosin (laminin 2) with very late activation antigen‐6 is necessary for the survival of CD4+ CD8+ immature thymocytes , 2000, Immunology.

[7]  H. Nagawa,et al.  α6β1 Integrin (VLA-6) Mediates Leukocyte Tether and Arrest on Laminin under Physiological Shear Flow , 2000 .

[8]  K. Tryggvason,et al.  Erythromegakaryocytic Cells Synthesize Laminin-8 (α4β1γ1) , 2000 .

[9]  E. Forsberg,et al.  Restricted distribution of laminin α1 chain in normal adult mouse tissues , 1999 .

[10]  E. Engvall,et al.  Blood Platelets Contain and Secrete Laminin-8 (α4β1γ1) and Adhere to Laminin-8 via α6β1 Integrin , 1999 .

[11]  R. Pardi,et al.  Upregulation of Integrin 6/β1 and Chemokine Receptor CCR1 by Interleukin-12 Promotes the Migration of Human Type 1 Helper T Cells , 1999 .

[12]  V. Quaranta,et al.  Laminin 5 in the Human Thymus: Control of T Cell Proliferation via α6β4 Integrins , 1999, The Journal of cell biology.

[13]  A. Sonnenberg,et al.  Cre-loxP–mediated Inactivation of the α6A Integrin Splice Variant In Vivo: Evidence for a Specific Functional Role of α6A in Lymphocyte Migration but Not in Heart Development , 1998, The Journal of cell biology.

[14]  S. Nilsson,et al.  Immunofluorescence Characterization of Key Extracellular Matrix Proteins in Murine Bone Marrow In Situ , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[15]  U. Bergmann,et al.  Primary Structure, Developmental Expression, and Immunolocalization of the Murine Laminin α4 Chain* , 1997, The Journal of Biological Chemistry.

[16]  M. Okano,et al.  Differentiation-dependent expression of laminin-8 (α4β1γ1) mRNAs in mouse 3T3-L1 adipocytes☆ , 1997 .

[17]  S. Kröger,et al.  Developmental regulation of the laminin alpha5 chain suggests a role in epithelial and endothelial cell maturation. , 1997, Developmental biology.

[18]  R. Deutzmann,et al.  Cloning of the Mouse Laminin α4 cDNA. Expression in a Subset of Endothelium , 1997 .

[19]  J. Sanes,et al.  The Laminin α Chains: Expression, Developmental Transitions, and Chromosomal Locations of α1-5, Identification of Heterotrimeric Laminins 8–11, and Cloning of a Novel α3 Isoform , 1997, The Journal of cell biology.

[20]  G. Mayr,et al.  Integrin-mediated intracellular Ca2+ signaling in Jurkat T lymphocytes. , 1997, Journal of immunology.

[21]  A. Sonnenberg,et al.  Distribution of laminin variants and their integrin receptors in human secondary lymphoid tissue. Colocalization suggests that the alpha 6 beta 4-integrin is a receptor for laminin-5 in lymphoid follicles. , 1996, Cell adhesion and communication.

[22]  G. Pérez-Yarza,et al.  Presence of laminin and 67KDa laminin-receptor on endothelial surface of lung capillaries. An immunocytochemical study. , 1996, Histology and histopathology.

[23]  R. Kramer,et al.  Laminin 5 deposition promotes keratinocyte motility. , 1996, Experimental cell research.

[24]  F. Pope,et al.  The complete cDNA sequence of laminin alpha 4 and its relationship to the other human laminin alpha chains. , 1996, European journal of biochemistry.

[25]  J. Ritz,et al.  Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. , 1996, Experimental hematology.

[26]  H. Prentice,et al.  VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation. , 1995, Experimental hematology.

[27]  E. Castaños-Vélez,et al.  Extracellular matrix proteins and integrin receptors in reactive and non-reactive lymph nodes. , 1995, Immunology.

[28]  T. Springer,et al.  High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. , 1995, Immunology today.

[29]  H. Shibayama,et al.  Laminin and fibronectin promote the chemotaxis of human malignant plasma cell lines. , 1995, Blood.

[30]  K. Tryggvason,et al.  Primary structure and expression of a novel human laminin α4 chain , 1995 .

[31]  P. Friedl,et al.  T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules. , 1995, Journal of immunology.

[32]  E. Bloemena,et al.  Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B‐cell non‐Hodgkin lymphomas , 1995, Histopathology.

[33]  J. Coligan,et al.  Alpha 3 beta 1 and alpha 6 beta 1 integrins mediate laminin/merosin binding and function as costimulatory molecules for human thymocyte proliferation. , 1995, Journal of immunology.

[34]  C. Pucillo,et al.  Differential attachment of human neoplastic B cells to purified extracellular matrix molecules. , 1994, Blood.

[35]  T. K. van den Berg,et al.  Localization of beta 1 integrins and their extracellular ligands in human lymphoid tissues. , 1993, The American journal of pathology.

[36]  J. Coligan,et al.  Expression of merosin in the thymus and its interaction with thymocytes. , 1993, Journal of immunology.

[37]  W. Carter,et al.  Epiligrin, a component of epithelial basement membranes, is an adhesive ligand for alpha 3 beta 1 positive T lymphocytes , 1993, The Journal of cell biology.

[38]  M. Daha,et al.  Antineutrophil cytoplasmic autoantibodies: a review of the antigens involved, the assays, and the clinical and possible pathogenetic consequences. , 1993, Blood.

[39]  H. Cheung,et al.  Basement membrane and its components on lymphocyte adhesion, migration, and proliferation. , 1992, Journal of immunology.

[40]  L. Frati,et al.  Triggering through CD16 or phorbol esters enhances adhesion of NK cells to laminin via very late antigen 6 , 1992, The Journal of experimental medicine.

[41]  J. Kupiec-Weglinski,et al.  Lymphocyte traffic is modified in vivo by anti-laminin antibody. , 1991, Immunology.

[42]  E. Saksela,et al.  Fibronectin facilitates the migration of human natural killer cells , 1991, European journal of immunology.

[43]  K. Horgan,et al.  Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. , 1990, Journal of immunology.

[44]  K. Horgan,et al.  Regulated expression and binding of three VLA (β1) integrin receptors on T cells , 1990, Nature.

[45]  C. Morimoto,et al.  Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex , 1989, The Journal of experimental medicine.

[46]  R. Testi,et al.  Laminin synthesis by NK cells and modulation of its expression by TPA (12-O-tetradecanoylphorbol-13-acetate). , 1989, Experimental cell research.

[47]  J. Varani,et al.  Laminin receptor expression on murine tumor cells: Correlation with sensitivity to natural cell‐mediated cytotoxicity , 1989, International journal of cancer.

[48]  I. Ernberg,et al.  Absence, or low expression, of leukocyte adhesion molecules CDI1 and CD18 on burkjtt lymphoma cells , 1988, International journal of cancer.

[49]  A. Maghazachi,et al.  Lymphokine-activated killer cells in rats. III. A simple method for the purification of large granular lymphocytes and their rapid expansion and conversion into lymphokine-activated killer cells , 1988, The Journal of experimental medicine.

[50]  M. Pierschbacher,et al.  T-lymphocyte differentiation and the extracellular matrix: identification of a thymocyte subset that attaches specifically to fibronectin. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[51]  J. Varani,et al.  Laminin inhibits the recognition of tumor target cells by murine natural killer (NK) and natural cytotoxic (NC) lymphocytes. , 1985, The American journal of pathology.

[52]  C. Gahmberg,et al.  Identification of a Cell Surface Protein Complex Mediating Phorbol Ester‐Induced Adhesion (Binding) among Human Mononuclear Leukocytes , 1985, Scandinavian journal of immunology.

[53]  J. Varani,et al.  Expression of a laminin-like substance on the surface of murine natural killer (NK) lymphocytes and its role in NK recognition of tumor target cells. , 1985, Journal of immunology.

[54]  W. Savino,et al.  Extracellular matrix of the human thymus: immunofluorescence studies on frozen sections and cultured epithelial cells. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[55]  M. Wicha,et al.  Macrophages express cell surface laminin. , 1983, Experimental cell research.

[56]  J. Watson,et al.  Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line , 1980, The Journal of experimental medicine.

[57]  J. Jönsson,et al.  Characterization of Bone Marrow Laminins and Identification of 5-Containing Laminins as Adhesive Proteins for Multipotent Hematopoietic FDCP-Mix Cells , 1999 .

[58]  P. Ekblom,et al.  Identification of laminin-10/11 as a strong cell adhesive complex for a normal and a malignant human epithelial cell line. , 1999, Journal of cell science.

[59]  H. Schnaper,et al.  12-O-tetradecanoylphorbol 13-acetate stimulates human T-lymphocyte adherence to the fibronectin RGD domain and the laminin IKVAV domain. , 1994, Cellular immunology.

[60]  I. Cohen,et al.  Extracellular matrix induces tumour necrosis factor-alpha secretion by an interaction between resting rat CD4+ T cells and macrophages. , 1993, Immunology.

[61]  B. Imhof,et al.  Mechanisms of thymus homing. , 1993, Blood.