Table Of ContentCurrent Topics in
Microbiology
and Immunology
181
Editors
R. W. Com pans, Birmingham/Alabama' M. Cooper,
Birmingham/Alabama' H. Koprowski, Philadelphia
I. McConnell, Edinburgh F. Melchers, Basel
V. Nussenzweig, New York' M. Oldstone,
La Jolla/California . S. Olsnes, Oslo . M. Potter,
Bethesda/Maryland H. Saedler, Cologne . P. K. Vogt,
Los Angeles . H. Wagner, Munich I. Wilson,
La Jolla/California
Macrophage Biology
and Activation
Edited by S.W. Russell and S. Gordon
With 42 Figures
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
STEPHEN W. RUSSELL
Wilkinson Distinguished Professor
and Director
University of Kansas Cancer Ctr.
Kansas City, KA 66160-7312
USA
SIAMON GORDON
Sir William Dunn School of Pathology
University of Oxford
South Parks Road
Oxford OX1 3RE
U.K.
Cover illustration: See page 8, Fig. 1i .
ISBN-13: 978-3-642-77379-2 e-ISBN-13: 978-3-642-77377-8
001: 10.1007/978-3-642-77377-8
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© Springer-Verlag Berlin Heidelberg 1992
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Preface
The amazing world of the mononuclear phagocyte keeps ex
panding at a pace that, in current vernacular, is truly awesome.
As a result, maintaining currency with the latest developments
and controversies that pertain to this cell type is becoming
increasingly difficult. Hopefully, what is contained in this
volume will be of help in this regard.
The topics have been selected to provide an overview of
subject areas that either have recently become much better
understood or are ones that, in our opinion, hold the promise
of new levels of understanding as they are developed in the
future. The scope of what is included ranges from how these
cells develop, through the means that are used to regulate
them, to the roles that they have in different tissues and in a
variety of infectious diseases.
In closing these brief introductory remarks, we want to
thank the contributors to this volume, especially those who
helped make our job easier by meeting their deadlines, and our
coordinator at Springer-Verlag, Ms. Marga Botsch.
STEPHEN W. RUSSELL and SIAMON GORDON
List of Contents
S. GORDON, L. LAWSON, S. RABINOWITZ, P. R. CROCKER,
L. MORRIS, and V. H. PERRY:
Antigen Markers of Macrophage Differentiation
in Murine Tissues ................. .
J. S. HUNT and J. W. POLLARD:
Macrophages in the Uterus and Placenta. 39
J.-D. VASSALLI, A. WOHLWEND, and D. BELIN:
Urokinase-Catalyzed Plasminogen Activation
at the Monocyte/Macrophage Cell Surface:
A Localized and Regulated Proteolytic System. 65
D. A. RAPPOLEE and Z. WERB:
Macrophage-Derived Growth Factors. 87
P. ROTH and E. R. STANLEY:
The Biology of CFS-1 and Its Receptor. .. 141
T.-Y. CHEN, M.-G. LEI, T. SUZUKI, and D. C. MORRISON:
Lipopolysaccharide Receptors and Signal Transduction
Pathways in Mononuclear Phagocytes . . . . . . . . .. 169
A. ADEREM:
The Role of Myristoylated Protein Kinase C Substrates
in Intracellular Signaling Pathways. . . . . . . . . . .. 189
L. VARESIO, D. RADZIOCH, B. BOHAZZI, and G. L. GUSELLA:
Ribosomal RNA Metabolism in Macrophages. . 209
M. S. MELTZER and H. E. GENDELMAN:
Mononuclear Phagocytes as Targets,
Tissue Reservoirs, and Immunoregulatory Cells
in Human Immunodeficiency Virus Disease. ..... 239
M. A. HORWITZ:
Interactions Between Macrophages
and Legionella pneumophila . . . . . . . . . . . . . . .. 265
VIII List of Contents
R. A. B. EZEKOWITZ:
Chronic Granulomatous Disease: An Update and a
Paradigm of the Use of Interferon-y as Adjunct
Immunotherapy in Infectious Diseases. . . . . . . . . .. 283
List of Contributors
(Their addresses can be found at the beginning of their respec
tive chapters)
ADEREM, A. 189 MORRIS, L. · .. 1
BELIN, D. . . 65 MORRISON, D. C. 169
BOHAZZI, B. 209 PERRY, V. H. . . 1
CHEN, T.-Y. 169 POLLARD, J. W. 39
CROCKER, P. R. 1 RABINOWITZ, S. 1
EZEKOWITZ, R. A. B. 283 RADZIOCH, D. 209
GENDELMAN, H. E. 239 RAPPOLEE, D. A. 87
GORDON, S. . . 1 ROTH, P . . . . 141
GUSELLA, G. L. 209 STANLEY, E. R. 141
HORWITZ, M. A. 265 SUZUKI, T. · . 169
HUNT, J. S. 39 VARESIO, L. · . 209
LAWSON, L. VASSALLI, J.-D. 65
LEI, M. G. 169 WERB, Z . . . . 87
MEL TZER, M. S. 239 WOHLWEND, A. 65
Antigen Markers of Macrophage Differentiation
in Murine Tissues
S. GORDON. L. LAWSON, S. RABINOWITZ, P. R. CROCKER, L. MORRIS, and V. H. PERRY
Introduction ..
2 Antigen Markers. 3
2.1 F4/80 3
2.2 Complement Receptor, Type 3 (CR3) 4
2.3 7/4. 4
2.4 Sialoadhesin (SER) 4
2.5 FA.ll 5
3 Distribution and Turnover of Macrophages . 5
3.1 Ontogeny. 5
3.2 Normal Adult. . ...... 11
3.2.1 Expression of Antigen Markers by Tissue Macrophages. 13
3.3 Elicited and Activated Macrophages . 20
4 Relationship of Macrophages to Cells of Related Lineages. 24
5 Antigens and Macrophage Heterogeneity .. 27
6 Conclusion. 29
Appendix. 30
References. 32
1 Introduction
Cell-restricted membrane antigens have made it possible to map the distribution
of mature macrophages in many murine tissues. Monoclonal antibodies (mAbs)
have been used to define the appearance of macrophages dusing foetal and
postnatal development, to establish the anatomic relationships between macro
phages and other cells in the normal and diseased adult, and to investigate
cellular modulation and heterogeneity within different microenvironments.
Current studies have illustrated the complex differentiation pathway of mononu
clear phagocytes in vivo and have raised questions concerning the mechanisms
that determine monocyte entry, migration and fate within tissues. Macrophages
constitute a major, widely dispersed system of cells that regulate homeostasis in
the normal host and respond to tissue injury by contributing essential functions
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OXI 3RE,
United Kingdom
Current TopICS in Microbiology and Immunology, Vol. 181
© Springer-Verlag Berlin-Heidelberg 1992
'" V> Gl 0 C. 0 :J ~ ~
d
References AUSTYN and GORDON 1981 STARKEY et al. 1987 DRI and CROCKER, unpublishe SPRINGER et al. 1979 BELLER et al. 1982 ROSEN and GORDON 1987 HIRSCH and GORDON 1983 TREE, HiRSCH and RABINOWITZ, unpublished CROCKER and GORDON 1989 CROCKER, unpublished RABINOWITZ et al. 1991; RABINOWITZ, DA SILVA, MILON, STEINMAN and AUSTYN, unpublished
nd heterogeneity in murine tissues Comments Down-regulated in T-cell dependent areas. Polyclonal Ab is cytotoxic and cross-reacts with rat Ag. Leucocyte integrin. Both mAbs block iCb binding site; only 3blocks adhesion in vitro 5C6 and in vivo. Polymorphic, useful for PMN depletion, e.g. in bone marrow. Macrophage lectin for sialylated structures. Expression modulated by homologous plasma/serum inducer. Differential glycosylation (WGA binding) in exudate macrophages
a
d to define macrophage distribution Tissue distribution Mature macrophages PMNs, macrophages and NK cells Heterogeneity on macrophages in tissues PMNs and activated macrophages macrophages Stromal Macrophage and dendritic cell endosome membrane
e
s
u
antigens MW (kDa) ~150 150/90 ~40 185 85-90
n
ei
ane glycoprot Antibody (Ab) Rat mAb Rabbit polyclonal Rat mAb Ml/70 5C6 Rat mAb Rat mAb SER-4 Rabbit polyclonal Rat mAb FA.ll
br
Mem sin
e
1. n dh
Table Antige(Ag) F4/80 CR3 7/4 Sialoa FA.ll
Antigen Markers of Macrophage Differentiation in Murine Tissues 3
during inflammation and repair. In this review we consider several membrane
marker antigens which have proved useful in studying the life history and
biologic properties of macrophages, and relate immunochemical studies on
antigen expression to lineage analysis and macrophage differentiation in vivo.
We restrict our discussion to the mouse, in which it is possible to manipulate the
system in its entirety. Where known, properties of macrophages in other species
are broadly similar.
2 Antigen Markers
In this section we summarise the properties of antigens which we have used to
study macrophage populations in situ and in vitro. Table 1 lists features that are
relevant to their use as markers. Other mAbs that have been used to characterise
murine macrophages will be referred to in the text. Details of antigen expression
will be described and illustrated below and our standard protocol for immunocy
tochemical analysis is given in an appendix.
2.1 F4/80
Knowledge of the presence of mature macrophages in murine tissues derives
mainly from studies with mAbs and monospecific polyclonal antibodies directed
against the macrophage-specific plasma membrane differentiation antigen
F4!80. The epitope defined by a rat mAb isolated by AUSTYN and GORDON (1981)
proved stable to perfusion-fixation, thus permitting HUME, PERRY and others to
identify macro phages in a variety of tissues (for earlier reviews see HUME and
GORDON 1985; PERRY and GORDON 1988). Subsequently DRI (unpublished
observations) used affinity purified F4!80 antigen to raise a potent polyclonal
antiserum that reacts with additional epitopes on the F4!80 molecule. This
monospecific reagent enhances the detection of macrophage plasma mem
brane within tissues (LAWSON et al. 1990). The F4!80 antigen is a single chain
glycoprotein which displays microheterogeneity on Western blot analysis of
Iysates prepared from various tissues and cell lines. The molecule has been
purified (STARKEY et al. 1987) but not yet cloned and its function is unknown.
Expression of F4!80 by peritoneal macrophages is down-regulated by in
flammatory stimuli, which induce the recruitment of immature cells, by short-term
adhesion in cell culture and by exposure to Iymphokines, especially interferon-y
(GORDON et al. 1986a). However, the F4!80 antigen can be readily detected on
macrophages by immunocytochemistry after all these treatments. The labelling
pattern in isolated macrophages is mainly (>80%) at the plasma membrane
and is uniform over the cell surface, although F4!80 antigen expression is
concentrated in ruffles and at the edge of spreading cells.
