Human Mast Cells

115 Pages·1989·5.541 MB·English

by  Dr. Ann M. Dvorak (auth.)

Advances in Anatomy
Embryology and Cell Biology
Vol. 114
Editors
F. Beck, Leicester W Hild, Galveston
W Kriz, Heidelberg R. Ortmann, Kaln
J.E. Pauly, Little Rock T.H. Schiebler, Wiirzburg
Ann M. Dvorak
Human Mast Cells
With 89 Figures
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Dr. Ann M. Dvorak
Department of Pathology, Beth Israel Hospital
330 Brookline Avenue, Boston, MA 02215, USA
ISBN-13: 978-3-540-50374-3 e-ISBN-13: 978-3-642-74145-6
DOl: 10.1007/978-3-642-74145-6
Library of Congress Cataloging-in-Publication Data
Dvorak. Ann M. Human mast cells/Ann M. Dvorak.
p. cm.-(Advances in anatomy, embryology, and cell biology; vol. 114)
Bibliography: p.
ISBN-13: 978-3-540-50374-3 (U.S.)
1. Mast cells-Immunology. 2. Anaphylaxis-Pathogenesis. I. Title. II. Series:
Advances in anatomy, embryology, and cell biology; v. 114. QL80l.E67
vol. 114 [QRI85.8.M35] 574.4 s [616.07'9] 88-31849
This work is subject to copyright. All rights are reserved, whether the whole or part of the
material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data
banks. Duplication of this pUblication or parts thereof is only permitted under the
provisions of the German Copyright Law of September 9, 1965, in its version of June 24,
1985, and a copyright fee must always be paid. Violations fall under the prosecution act of
the German Copyright Law.
© Springer-Verlag Berlin Heidelberg 1989
The use of general descriptive names, trade names, trade marks, etc. in this publication,
even if the former are not especially identified, is not to be taken as a sign that such
names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly
be used freely by anyone.
Product Liability: The publisher can give no guarantee for information about drug dosage
and application thereof contained in this hook. In every individual case the respective user
must check its accuracy by consulting other pharmaceutical literature.
Typesetting: Macmillan India Ltd, Bangalore-25, India
2121/3140-54321O-Printed on acid-free paper
For my family
H aroid, John, Laurie, and Jane
Contents
1 Introduction
2 Ultrastructure of Human Mast Cells . 3
3 Ultrastructure of Human Basophils . 13
4 In Vitro Studies of Human Mast Cells 15
4.1 Human Mast Cell Granules and Lipid Bodies 15
4.1.1 Differences in Structure . . . . . . 15
4.1.2 Differences in Content. . . . . . . . . 15
4.1.3 Differences in Mechanism of Formation 21
4.1.4 Differences in Behavior During Degranulation 22
4.1.5 Differences in Behavior During Recovery from
Degranulation. . . . . . . . . . . . 25
4.2 Anaphylactic Degranulation of Human Lung Mast
Cells In Vitro. . . . . . . . . . . . .. 27
4.3 Recovery from Anaphylactic Degranulation of Human
Lung Mast Cells In Vitro. 48
4.3.1 Early Recovery Events. . 48
4.3.2 Late Recovery Events. . 65
4.3.3 Mixed Recovery Patterns. 72
5 In Vivo Studies of Human Mast Cells 74
5.1 Anaphylactic Degranulation of Human Mast Cells
In Vivo. . . . . . . . . . . . . " 74
5.2 Piecemeal Degranulation of Human Mast Cells
In Vivo. . . . . . . . . . . . . .. 75
5.3 Activated Human Mast Cells Have Increased Lipid.
Bodies . . . . . 81
5.4 Mast Cell Shedding. . . . 82
6 Mast Cell Morphologic Cycles 83
6.1 In Vitro . 83
6.2 In Vivo. . . . . . . . . 88
VII
7 Concluding Remarks 89
8 Summary 92
References . 95
Subject Index 101
VIII
1 Introduction
Mast cells and basophils were first described by Ehrlich (1877, 1878, 1879).
Although these cells share many functional properties, they can readily be
distinguished using morphological criteria (Dvorak 1986a; Dvorak et al. 1983a,
1983c; Galli et al. 1984). The identification of immunoglobulin E (IgE) and high
affinity IgE receptors on mast cells and basophils was instrumental to our
understanding of the mechanisms underlying the role of these cells in immediate
hypersensitivity reactions (Ishizaka and Ishizaka 1979; Ishizaka et al. 1966, 1972,
1973; Tomioka and Ishizaka 1971). We now know that these IgE-mediated
mechanisms as well as a number of other stimuli can cause the rapid release of many
preformed mediators of inflammation from both mast cells and basophils (Galli
et al. 1984). The most well-known of these is histamine. Potent mediators that are
not preformed are also stimulated and released from these cells. Recently, products
of arachidonic acid metabolism, such as the prostaglandins and leukotrienes, have
been found to be generated either by the cyclooxygenase pathway or the lipoxy
genase pathway in mast cells and basophils (Lewis and Austen 1981, 1984; Peters
et al. 1984, 1987). Detailed studies and reviews of the biochemistry of these
mediators and their immunologically mediated reactions have been published
(Lewis and Austen 1981, 1984; Lichtenstein et al. 1979; MacGlashan et al. 1982b;
Paterson et al. 1976; Peters et al. 1984, 1987).
Mast cells and basophils contain other important biochemicals. Both cells are
characterized by their prominent complement of metachromatic cytoplasmic
granules wherein reside various sulfated glycosaminoglycans (GAGS) (Galli et al.
1984). The most well-known of these is heparin (Metcalf et al. 1979). The various
other GAGS and their distribution in basophils and mast cells of a variety of species
form the subject of current intense investigation (reviewed in Galli et al. 1984).
Early histochemical studies identified the presence of certain human mast cell
enzymes. These included p-hexosaminidase, p-glucuronidase, and a trypsin-like
esterase (Chiu and Lagunoff 1972; Glenner and Cohen 1960; Montagna 1957).
More recently, biochemical analyses of isolated human lung mast cells have
documented the presence of mast cell-associated tryptase, p-hexosam~nidase,
p-glucuronidase, and aryl sulfatase (Schwartz et al. 1981 a, b, 1983).
Human mast cells, as recognized in their fully differentiated forms, are wide
spread in the connective tissues of virtually all organs in the body. They are
concentrated in organs which are potential portals of entry for foreign agents, such
as skin, lung, and gut. Mast cells also tend to be localized to perivascular structures
in these organs. They can, however, be found throughout tissues, including within
epithelia. Mast cells have the capacity to migrate and to proliferate and have been
found in increased numbers in the tissues of patients with a wide variety of diseases.
These disorders include chronic inflammatory disorders, cell-mediated immu
nologic disorders, such as contact allergy, and neoplastic events of non-mast cell
origin. Mast cell-specific disorders such as urticaria pigmentosa and systemic
mastocytosis are characterized by extraordinary increases in mast cells in human
tissues. For example, normal human skin mast cell counts vary between 5120 and
9472 per cubic millimeter (Mikhail and Miller-Milinska 1964). These values may be
as high as 260000 to 380000 per cubic millimeter of skin in mastocytosis (Mikhail
and Miller-Milinska 1964). Despite this, little to nothing is currently known
regarding the functional role(s) of mast cells in these diseases. Moreover, little to
nothing is known regarding the physiological role(s) of mast cells in health. Perhaps
because so little is really known about the function of mast cells in health and
disease, as well as the esthetic appeal of these cells, investigators continue to pursue
their elusive functional capacities. It hardly seems likely that mast cells and
basophils exist to plague people with sneezing, scratching, and wheezing episodes,
or to kill us by anaphylaxis.
Because knowledge of structure frequently precedes knowledge of function, and
is essential for elucidating structure-function relationships, we herein review the
structural information that is available for human mast cells. We first will itemize
the differential diagnostic criteria for human basophils and human mast cells to
assure the correct identification of these very similar cells. The in vivo ultrastruc
tural anatomy of normal human mast cells from all available sites will be
considered. Recent technological developments have made the isolation, purifi
cation, and short-term culture of human mast cells from a variety of tissue sites
possible (MacGlashan et al. 1982a). These sites include lung (Caulfield et al. 1980;
Ishizaka et al. 1983; Paterson et al. 1976; Schulman et al. 1982, 1983), gut (Fox et al.
1985), and adenoids (Behrendt et al. 1978). Such preparations of human mast cells
have made it possible to do structure-function studies on aliquots of the same mast
cell preparations in vitro (Behrendt et al. 1978; Caulfield et al. 1980; Dvorak et al.
1983d, 1984, 1985d, 1986, 1987, 1988; Hammel et al. 1985). We will review the
current state of these studies which includes analysis of mast cell organelles by a
variety of ultrastructural techniques (Dvorak et al. 1983d, 1984; Hammel et al.
1985), of anaphylactic degranulation (Behrendt et al. 1978; Caulfield et al. 1980;
Dvorak et al. 1984, 1985d), and recovery from degranulation (Dvorak et al. 1986,
1987, 1988). Other studies have utilized isolated skin slices for observations
regarding mast cell release reactions (Greaves et al. 1972; Pearce et al. 1974; Tharp
et al. 1983). Finally, we will review the available ultrastructural data in vivo
implicating functioning mast cells in a variety of disorders (Galli et al. 1984). These
studies include anaphylactic degranulation of mast cells in skin (Dvorak et al.
1976c; Kobayasi and Asboe-Hansen 1969a; Lepow et al. 1970; Yancey e,t al. 1985),
heart (Dvorak 1986b), synovium (Wynne-Roberts and Anderson 1978), and
piecemeal degranulation of mast cells (Galli and Dvorak 1984; Galli et al. 1984) in
many human diseases involving a variety of organs (Colvin et al. 1974; Dvorak
1979; Dvorak and Dickersin 1979; Dvorak and Monahan 1985a; Dvorak et al.
1974, 1976c, 1978, 1980c,d, 1982; Galli and Dvorak 1984).
2
2 Ultrastructure of Human Mast Cells
The ultrastructural anatomy of human mast cells has been described in numerous
tissues. These sites include the following: skin (Asboe-Hansen 1971; Barnett 1975;
Bowyer 1968; Burns and Hoak 1975; Dvorak et al. 1976c, 1980c, 1982; Fedorko and
Hirsch 1965; Fujita et al. 1972; Hashimoto et al. 1966; Hibbs et al. 1960; Kobayasi
and Asboe-Hansen 1969a, 1969b; Moriyasu and Yamura 1973; Naveh et al. 1975;
Orr 1977; Pasyk et al. 1983; Trotter and Orr 1974; Yancey et al. 1985); lung
(Brinkman 1968; Caulfield et al. 1980; Dvorak et al. 1983d, 1984, 1985d, 1986, 1987,
1988; Fox et al. 1981; Hammel et al. 1985; Kobayasi et al. 1968; Orr 1977; Parmley
et al. 1975; Paterson et al. 1976; Ts'ao et al. 1977); bronchiole mucosa (Brinkman
1968; Trotter and Orr 1973; Ts'ao et al. 1977); nose (Taraska and Deno 1973;
Trotter and Orr 1974); adenoids (Behrendt et al. 1978); lymph node (Parmley et al.
1975); bone marrow (Ts'ao et al. 1977); gingiva (Barnett 1973, 1975; Kobayasi et al.
1968; Weinstock and Albright 1967); stomach (Dobbins et al. 1969; Hibbs et al.
1960; Steer 1976); small bowel (Dobbins et al. 1969; Dvorak 1979; Dvorak and
Dickersin 1979; Dvorak et al. 1978, 1980d; Rao 1973); colon (Dobbins et al. 1969;
Fox et al. 1985); liver (Naveh et al. 1975); synovium (Wynne-Roberts and Anderson
1978); peripheral nerve (Pineda 1965); iris (Nii et al. 1974); heart (Dvorak 1986b);
kidney (Colvin et al. 1974; Dvorak and Monahan 1985a). Human mast cells are
readily recognized by electron microscopy. The only cell with which they may be
confused is the basophil (see Sect. 3). Criteria for identification of mast cells in
human tissues (Fig. 1) include a monolobed nucleus, surface architecture composed
of narrow, elongated folds, the presence of typical cytoplasmic granules, and the
absence of cytoplasmic glycogen aggregates. The cytoplasm also contains mito
chondria, free ribosomes, intermediate filaments, and lipid bodies. Golgi areas are
small in mature cells and membrane-bound ribosomes are rare in mature and
imma ture cells. 1
I Human mast cells from various in vivo sources and in vitro experiments are presented following a
variety of ultrastructural methods which illustrate different aspects of mast cell biology. The images,
therefore, demonstrate variability, depending on the technique used. These methods and abbreviations
for them are listed here. Abbreviations are used in individual legends to identify the specific method used
to produce that image. All methods are described in primary publications in the references (Dvorak et al.
1972c, 1980b, 1981a, 1983b, 1983d, 1985b).
1. Osmium-collidine uranyl en bloc (OCUB)
2. Osmium potassium ferrocyanide (OPF)
3. Cationized ferritin (CF)
4. 3H-Arachidonic acid autoradiography eH-AA)
5. 3sS-Radiolabeled sulfur autoradiography eSS)
6. Endogenous peroxidase cytochemistry demonstrated with the substrate diaminobenzidine (DAB).
3
Fig. l. Human mast cell in vivo from a breast fibroadenoma shows a monolobed nucleus, narrow
surface folds, and numerous cytoplasmic granules. OeUB, X 14500
Mature mast cell granules are smaller, vary more in shape, are more numerous,
and generally contain more complex substructural patterns than the granules of
basophils. Most observers have described several of the prevalent mast cell granule
patterns in their individual works. Examination of all published micrographs as
well as human mast cells from nearly all tissue sites (A.M. Dvorak, unpublished
data) provides a working description of granule patterns. Different terms have been
used by various authors to identify identical granule patterns. General agreement
exists, however, among the published micrographs. We (Dvorak et al. 1984) and
others refer to the four basic granule patterns of human mast cells as scrolls
(Fig. 2A) (Asboe-Hansen 1971; Barnett 1973; Bowyer 1968; Brinkman 1968; Burns
and Hoak 1975; Caulfield et al. 1980; Colvin et al. 1974; Dobbins et al. 1969; Dvorak
1979, 1986b; Dvorak and Dickersin 1979; Dvorak and Monahan 1985a; Dvorak
et al. 1978, 1980c, d, 1982, 1983d, 1984, 1985d, 1986, 1988; Fox et al. 1981 ; Fox et al.
1985; Fujita et al. 1969; Hammel et al. 1985; Hashimoto et al. 1966; Kawanami et al.
1979; Kobayasi and Asboe-Hansen 1969b; Kobayasi et al. 1968; Moriyasu and
Yamura 1973; Naveh et al. 1975; Nii et al. 1974; Orr 1977; Parmley et al. 1975;
Pasyk et al. 1983; Paterson et al. 1976; Pineda 1965; Rao 1973; Steer 1976; Trotter
and Orr 1974; Ts'ao et al. 1977; Weinstock and Albright 1967), cryst~ls (Asboe
Hansen 1971; Burns and Hoak 1975; Caulfield et al. 1980; Dobbins et al. 1969;
Dvorak and Dickersin 1979; Dvorak et al. 1976c, 1980c, d, 1982, 1983d, 1984,
1985d, 1986, 1988; Fedorko and Hirsch 1965; Fox et al. 1985; Hashimoto et al. 1966;
Kawanami et al. 1979; Kobayasi and Asboe-Hansen 1969b; Kobayasi et al. 1968;
Moriyasu and Yamura 1973; Orr 1973, 1977; Parmley et al. 1975; Pasyk et al. 1983;
Trotter and Orr 1974; Ts'ao et al. 1977; Weinstock and Albright 1967), particles
(Fig. 2B) (Asboe-Hansen 1971; Brinkman 1968; Colvin et al. 1974; Dobbins et al.
4