Focal adhesion molecules expression and fibrillin deposition by lymphatic and blood vessel endothelial cells in culture.

The microfibrils of anchoring filaments, a typical ultrastructural feature of initial lymphatic vessels, consist mainly of fibrillin and are similar to the microfibrils of elastic fibers. As we previously demonstrated, they radiate from focal adhesions of lymphatic endothelium to the perivascular elastic network. Although present in large blood vessels, fibrillin microfibrils have never been detected in blood capillaries. Here we report immunohistochemical evidence that cultured bovine aortic and lymphatic endothelial cells express fibrillin microfibrils. These microfibrils form an irregular web in lymphatic endothelial cells, whereas in blood vessel endothelial cells they are arranged in a honeycomb pattern. Cultured lymphatic and blood vessel endothelial cells also produce focal adhesion molecules: focal adhesion kinase, vinculin, talin, and cytoskeletal beta-actin. Our data suggest that anchoring filaments of initial lymphatic vessels in vivo may be produced by endothelium. Through their connection with focal adhesions, they may form a mechanical anchorage for the thin wall of initial lymphatic vessels and a transduction device for mechanical signals from the extracellular matrix into biochemical signals in endothelial cells. The complex anchoring filaments-focal adhesions may control the permeability of lymphatic endothelium and finely adjust lymph formation to the physiological conditions of the extracellular matrix. The different deposition of fibrillin microfibrils in blood vessel endothelial cells may be related to the necessity of withstanding shear forces. Thus, in our opinion, differences in fibrillin deposition imply a different role of fibrillin in blood vessel and lymphatic endothelium.

[1]  R. Timpl,et al.  Cell adhesion and integrin binding to recombinant human fibrillin‐1 , 1996, FEBS letters.

[2]  J. Burke,et al.  ULTRASTRUCTURAL STUDIES ON THE LYMPHATIC ANCHORING FILAMENTS , 1968, The Journal of cell biology.

[3]  E. Davis Immunolocalization of microfibril and microfibril-associated proteins in the subendothelial matrix of the developing mouse aorta. , 1994, Journal of cell science.

[4]  J. Parsons,et al.  Signal transduction through integrins: A central role for focal adhesion kinase? , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[5]  D. Keene,et al.  [2] Fibrillin: Monomers and microfibrils , 1994 .

[6]  P. Byers,et al.  Marfan syndrome: defective synthesis, secretion, and extracellular matrix formation of fibrillin by cultured dermal fibroblasts. , 1992, The Journal of clinical investigation.

[7]  R. Lillie,et al.  THE OXYTALAN FIBER: A PREVIOUSLY UNDESCRIBED CONNECTIVE TISSUE FIBER , 1958, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[8]  C. Turner,et al.  Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. , 1988, Annual review of cell biology.

[9]  M. Rothkegel,et al.  The molecular architecture of focal adhesions. , 1995, Annual review of cell and developmental biology.

[10]  M. Lewis,et al.  Endothelial function in Marfan syndrome: selective impairment of flow-mediated vasodilation. , 1999, Circulation.

[11]  R. Gerli,et al.  Ultrastructural cytochemistry of anchoring filaments of human lymphatic capillaries and their relation to elastic fibers. , 1991, Lymphology.

[12]  W. Reutter,et al.  Focal adhesion kinase pp125FAK and the beta 1 integrin subunit are constitutively complexed in HaCaT cells. , 1998, Experimental cell research.

[13]  C. Kielty,et al.  Synthesis and assembly of fibrillin by fibroblasts and smooth muscle cells. , 1993, Journal of cell science.

[14]  F. Fauvel-Lafève,et al.  Microfibrils from the arterial subendothelium. , 1999, International review of cytology.

[15]  E. Engvall,et al.  Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils , 1986, The Journal of cell biology.

[16]  G. Sacchi,et al.  The structure of superficial lymphatics in the human thigh: precollectors , 1997, The Anatomical record.

[17]  E. Weber,et al.  Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. , 2000, Lymphology.

[18]  J. Parsons,et al.  A mechanism for regulation of the adhesion-associated protein tyrosine kinase pp125FAK , 1996, Nature.

[19]  G. Sacchi,et al.  Lymphatic vessels of the human heart: precollectors and collecting vessels. A morpho-structural study. , 1999, Journal of submicroscopic cytology and pathology.

[20]  M. Fruschelli,et al.  An immunological correlation between the anchoring filaments of initial lymph vessels and the neighboring elastic fibers: a unified morphofunctional concept. , 1997, Lymphology.

[21]  J. Parsons,et al.  pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Rosenbloom,et al.  Extracellular matrix 4: The elastic fiber , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  M. Herlyn,et al.  Heparin/endothelial cell growth supplement regulates matrix gene expression and prolongs life span of vascular smooth muscle cells through modulation of interleukin-1 , 1999, In Vitro Cellular & Developmental Biology - Animal.

[24]  R. Gerli,et al.  Morphometric analysis of elastic fibers in human skin lymphatic capillaries. , 1989, Lymphology.

[25]  A. Becker,et al.  Extracellular matrix of the human aortic media: An ultrastructural histochemical and immunohistochemical study of the adult aortic media , 2000, The Anatomical record.

[26]  Rocco,et al.  Abnormal morphology of fibrillin microfibrils in fibroblast cultures from patients with neonatal Marfan syndrome. , 1995, The American journal of pathology.

[27]  U. Francke,et al.  Dermal fibroblast culture as a model system for studies of fibrillin assembly and pathogenetic mechanisms: defects in distinct groups of individuals with Marfan's syndrome. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[28]  G. Cotta-Pereira,et al.  Oxytalan, elaunin, and elastic fibers in the human skin. , 1976, The Journal of investigative dermatology.

[29]  A. Aplin,et al.  Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. , 1998, Pharmacological reviews.

[30]  R. Pyeritz,et al.  Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. , 1990, The New England journal of medicine.

[31]  U. Francke,et al.  Quantitative differences in biosynthesis and extracellular deposition of fibrillin in cultured fibroblasts distinguish five groups of Marfan syndrome patients and suggest distinct pathogenetic mechanisms. , 1994, The Journal of clinical investigation.

[32]  J. Casley‐Smith Are the initial lymphatics normally pulled open by the anchoring filaments? , 1980, Lymphology.

[33]  A. Evdokiou,et al.  Expression of fibrillins and other microfibril-associated proteins in human bone and osteoblast-like cells. , 2000, Bone.

[34]  R. Gerli,et al.  A fibrillar elastic apparatus around human lymph capillaries , 2004, Anatomy and Embryology.

[35]  R. Glanville,et al.  Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. , 1991, The Journal of biological chemistry.

[36]  R. Mecham,et al.  Characterization of an in vitro model of elastic fiber assembly. , 1999, Molecular biology of the cell.

[37]  C. Turner,et al.  Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly , 1992, The Journal of cell biology.

[38]  J. Rosenbloom,et al.  Cell-type Specific Recognition of RGD- and Non-RGD-containing Cell Binding Domains in Fibrillin-1 (*) , 1996, The Journal of Biological Chemistry.