Table Of ContentConnective
Tissue
in
Health and Disease
Editor
Marcos Rojkind
Professor
Departments of Medicine and Pathology
Liver Research Center
Albert Einstein College of Medicine
Bronx, New York
First published 1990 by CRC Press
Taylor & Francis Group
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Reissued 2018 by CRC Press
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PREFACE
Frequently consider the connection of all things in the universe and their relation to one another. For
in a manner all things are implicated with one another, and all in this way are friendly to one another; for
one thing comes in order after another, and this is by virtue of the active movement and mutual conspiration
and the unity of the substance.
The Meditations of Marcus Aurelius
The connective tissues are composed of cells and a rich extracellular matrix. The latter
is complex and contains collagens, noncollagenous proteins and glycosaminoglycans. Dif
ferent connective tissues contain different types of cells and variable quantities of extracellular
matrix components. The compostion of the connective tissue as well as the tridimensional
organization of its components is made to fit the structure of the tissue and, accordingly,
there are significant qualitative and quantitative difrferences in the various tissues.
For many years it was considered that the connective tissue was a kind of glue made
by mesenchymal cells, and whose function was to hold together the different cellular elements
of a given tissue. Now, our concept of the connective tissue, and in particluar of the
extracellular matrix, has changed drastically.
We have learned that the extracellular matrix forms a radar system that maintains the
cells informed of the changes occurring in the microenvironment. The molecules that conform
the extracellular matrix are in communication with each other and with similar molecules
that conform the extracellular matrix are in communication with each other and with similar
molecules that are associated with the cell surface or that are integral components of the
plasma membrane. By this extensive mesh of multiple interactions, the extracellular matrix
establishes contact with the cytoskeleton. The extracellular matrix is made by the different
cells that compose the tissue. Its results from a complex network of signals that act by
autocrine and paracrine mechanisms and indicate each cells the amount and type of matrix
components to be produced. Accordingly changes in the types or amounts of cells, or in
the cytokines that regulate the expression of the cells will result in abnormal deposition of
matrix components. Moreover, the abnormal matrix will strongly influence the phenotypic
expression of the cells in the surroundings.
The complexity of the matrix components, of their effects on gene expression, and of
the cytokines that provide the signals that regulate extracellular matrix production are the
topics of the series on Connective Tissue in Health and Disease. We shall try to cover the
topics as they develop, but more importantly, to cover the gap between the basic apsects of
the connective tissue structure and function and its implications in disease. We shall attempt
to analyze animal models of human connective tissue diseases, describe recently developed
methodologies that may prove to be useful for the aficionados. Experts in the field will
review the composition and orginization of the extracellular matrix of specific organs. They
will describe the biological activities of the different connective tissue cells and will analyze
in great detail the cytokines and growth factors that modify cell proliferation and extracellular
matrix production.
We are aware of the limitations of books, mainly the short half-life of the printed
information. Therefore, when appropriate, the same topic may be discussed again in future
issues. The editor and the members of the advisory board will attempt to maintain the proper
balance of contents of this series. To publish issues that contain topics of scientific merit
and of clinical relevance.
Marcos Rojkind
July 1989
THE EDITOR
Marcos Rojkind, M.D., Ph.D. is a professor of medicine and pathology and a member
of the Liver Research Center at Albert Einstein College of Medicine in New York.
In 1960 he received an M.D. from the School of Medicine of the National University
of Mexico. He completed his training in pathology in the Pathology Unit of the General
Hospital under Professor Ruy Perez-Tamayo. He received a Helen Hay Whitney Foundation
Fellowship and from 1962 to 1965 he received training in biochemistry, in the Department
of Biochemistry, Albert Einstein College of Medicine, under Paul M. Gallop. In 1971 he
received a Ph.D. degree in Biochemistry from the Centro de Investigación y Estudios
Avanzados in Mexico City.
From 1966 to 1967 he was a senior investigator of the Department of Biochemistry, at
the Instituto Nacional de la Nutrición in Mexico. From 1967 to 1970 he was the chariman
of the Department. From 1970 to 1975 he was Professor of the Department of Cell Biology
of the Centro de Investigación y de Estudios Avanzados in Mexico. From 1975 to 1976 he
was visiting professor of medicine and biochemistry at Albert Einstein College of Medicine,
and from 1976 to 1978 he was associate professor of medicine and biochemistry at the above
mentioned institution. He returned to Mexico and from 1978 to 1986 he was professor of
biochemistry at the Centro de Investigación y de Estudios Avanzados del I.P.N.
Dr. Rojkind has over 100 publications in journals and books, and has participated in
many national and international meetings and has trained many scientists. He was the
president of the Mexican Association for the Study of the Liver from 1985 to 1986. In
collaboration with Dr. Joan Rodes and Roberto Groszmann, Dr. Rojkind founded and
organized the First Symposium International Hispanoparlante De Hepatologia in 1982. They
are currently organizing the fourth Symposium.
His major interest is the connective tissue of the liver, including the mechanisms leading
to cirrhosis and the mechanism of action of colchicine as an antifibrogenic agent. He is also
interested in the mechanisms by which pathogenic strains of Entamoeba histolytica invade
tissues.
ADVISORY BOARD
Olga O. Blumenfeld, Ph.D. Kari I. Kivirikko, M.D., Ph.D.
Professor Professor and Chairman
Department of Biochemistry Department of Medical Biochemistry
Albert Einstein College of Medicine University of Oulu
Yeshiva University Oulu, finland
Bronx, New York
Yutaka Nagai, Ph.D.
Peter H. Byers, M.D. Professor
Professor Department of Tissue Physiology
Department of Pathology Medical Research Institute
University of Washington Tokyo Medical and Dental University
Seattle, Washington Tokyo, Japan
Jean-Alexis Grimaud, Ph.D. Ruy Perez-Tamayo, M.D.
Director, Laboratoire de Pathologie Head and Professor
Cellulaire Sub-Division de Medicina Experimental
Institut Pasteur Facultad de Medicina, UNAM
Lyon Cedex, France Mexico City, Mexico
L. C. U. Junqueira, M.D. Sam Seifter, Ph.D.
Professor Professor
Department of Histology Department of Biochemistry
University of São Paulo Albert Einstein College of Medicine
São Paulo, Brasil Bronx, New York
Sharon M. Wahl, Ph.D.
Chief
Department of Cellular Immunology
National Institutes of Health
Bethesda, Maryland
CONTRIBUTORS
Mark J. Czaja, M.D. Juha Risteli, M.D., Ph.D.
Assistant Professor Collagen Research Unit
Department of Medicine Biocenter and Department of Medical
Albert Einstein College of Medicine Biochemistry
Bronx, New York University of Oulu
Oulu, Finland
Lynetta J. Freeman, M.S.
Senior Scientist-Veterinary Surgeon
Ethicon Research Foundation Leila Risteli, M.D., Ph.D.
Ethicon Inc. Collagen Research Unit
Sommerville, NJ Biocenter and Department of Medical
Biochemisty
University of Oulu
Jean-Alexis Grimaud, M.D. Ph.D. Oulu, Finland
Director
Laboratoire de Pathologie Cellulaire
Institut Pasteur Moisés Selman Lama, M.D.
Lyon Cedex, France Head
Clinical Research Division
Gerald A. Hegreberg, D.V.M., Ph.D. National Institute of Respiratory
Associate Professor Diseases
Department of Veterinary Microbiology Mexico City, Mexico
and Pathology
Washington State University
Pullman, Washington
Francis R. Weiner, M.D.
Simone Peyrol Assistant Professor
Laboratoire de Pathologie Cellulaire Department of Medicine
Institut Pasteur Albert Einstein College of Medicine
Lyon Cedex, France Bronx, New York
Mark A. Zern, M.D.
Director
Division of Gastroenterology
Roger Williams General Hospital
Associate Professor of Medicine
Brown University
Providence, Rhode Island
TABLE OF CONTENTS
Chapter 1
Immunolocalization of Connective Matrix Components. Methodological Approach, Limits,
and Significance in the Liver................................................................................................. 1
Jean-Alexis Grimaud and Simone Peyrol
Chapter 2
Animal Models of Connective Tissue Diseases....................................................................17
Gerald A. Hegreberg and Lynetta J. Freeman
Chapter 3
Noninvasi ve Methods for Detection of Organ Fibrosis........................................................61
Leila Risteli and Juha Risteli
Chapter 4
The Use of Molecular Hybridization Techniques as Tools to Evaluate Hepatic
Fibrogenesis.............................................................................................................................99
Mark A. Zern, Mark J. Czaja, and Francis R. Weiner
Chapter 5
Pulmonary Fibrosis: Human and Experimental Disease.....................................................123
Moisés Selman Lama
Index......................................................................................................................................189
Volume / 1
Chapter 1
IMMUNOLOCALIZATION OF CONNECTIVE MATRIX
COMPONENTS: METHODOLOGICAL APPROACH, LIMITS, AND
SIGNIFICANCE IN THE LIVER
Jean-Alexis Grimaud and Simone Peyrol
TABLE OF CONTENTS
I. Introduction..................................................................................................................2
II. Techniques for Immunolocalization of Hepatic Connective Matrix
Components: Methodological Strategy.....................................................................2
A. The Performance of the Antibodies................................................................3
B. Antigenic Preservation and Tissue Fixation..................................................3
C. Demasking the Antigen....................................................................................6
D. Visualizing the Immune Complex with Specificity.......................................7
III. Significance of Connective Matrix Immunolabeling..................................................7
A. Matrix Protein Distribution and Tissular Compartments...............................7
B. Matrix Protein Polymorphism: Electron Microscopic
Visualization in Extra- and Intracellular Compartments...............................8
C. Fibronectin — Ubiquitous and Permanent Molecule in the
Matrix Edifice..................................................................................................9
D. Codistribution of Interstitial Collagens and Patterns of
Connective Matrix Organization.....................................................................9
References 15
