The Hemopoietic Colony-Stimulating Factors: From Biology to Clinical Applications

Frontmatter......Page 1
Contents......Page 9
Preface......Page 13
1 - Historical introduction......Page 15
2 - General introduction to hemopoiesis......Page 24
Stem cells......Page 26
Dividing and maturing populations......Page 28
General regulation of hemopoiesis......Page 30
Stromal control of hemopoiesis......Page 33
Hemopoietic regulators......Page 34
Unresolved problems concerning hemopoiesis......Page 42
Identification and enumeration of stem cells......Page 47
Progenitor cell assays......Page 49
Long-term marrow cultures......Page 50
Serum-free versus serum-containing cultures......Page 51
Significance and limitations of bioassays for stem and progenitor cells......Page 52
Assays for hemopoietic growth factors......Page 53
Tests for direct action of a regulator......Page 56
Purification of factors......Page 57
GM-CSF......Page 58
G-CSF......Page 64
M-CSF (CSF-1)......Page 69
Multi-CSF(IL-3)......Page 75
Conclusions......Page 78
M-CSF receptor (c-fms)......Page 79
GM-CSF receptors......Page 88
Multi-CSF receptors......Page 91
G-CSF receptor......Page 96
Binding sites in the extracellular domains of the GM-CSF and Multi-CSF receptors......Page 99
Biological signaling by Multi-CSF and GM-CSF receptors......Page 101
Conclusions......Page 104
GM-CSF......Page 105
Multi-CSF (IL-3)......Page 109
G-CSF......Page 111
M-CSF......Page 115
GM-CSF and Multi-CSF receptor [GREEK SMALL LETTER ALPHA]-chains......Page 116
GM-CSF and Multi-CSF receptor [GREEK SMALL LETTER BETA]-chains......Page 117
G-CSF receptors......Page 118
M-CSF receptor (c-fms)......Page 121
Conclusions......Page 122
Proliferative stimulation......Page 123
Proliferative actions of specific CSFs......Page 146
Actions of other regulators in relation to CSF-stimulated cell proliferation......Page 158
Differentiation commitment......Page 163
Maturation induction......Page 168
Membrane transport and viability......Page 171
Functional activation......Page 172
General discussion......Page 176
8 - The biology of colony-stimulating factor production, degradation, and clearance......Page 180
Serum CSF levels......Page 182
Estimates of CSF concentrations available to act on hemopoietic cells......Page 186
Tissue and cellular sources of the CSFs......Page 189
Inductive signaling of CSF production......Page 194
Clearance and degradation of the CSFs......Page 198
Urine CSF levels......Page 199
Comment......Page 201
9 - Actions of the colony-stimulating factors in vivo......Page 202
Type of CSF for injection......Page 203
In vivo effects of injected CSF......Page 204
Synergistic actions between CSFs and other regulators......Page 214
Comment......Page 216
10 - Role of the colony-stimulating factors in basal hemopoiesis......Page 219
In vivo effects of CSF suppression......Page 220
Relative importance of the CSFs as regulators of granulocytes and macrophages......Page 223
11 - Actions of the colony-stimulating factors in resistance to infections......Page 225
Consequences of sustained excess levels of CSFs......Page 229
Actions of CSFs in immune responses and inflammatory states......Page 235
Disease states associated with abnormal CSF levels......Page 238
13 - The colony-stimulating factors and myeloid leukemia......Page 241
Growth of myeloid leukemic cells in vitro......Page 242
CSF levels in leukemia......Page 245
Autocrine production of CSF in myeloid leukemia......Page 246
Suppression of myeloid leukemias by CSFs......Page 251
Comment......Page 254
Adverse responses......Page 256
Cancer patients receiving chemotheraphy......Page 260
Chemotheraphy plus bone marrow transplantation......Page 262
Peripheral blood stem cell transplantation......Page 264
Cyclic neutropenia......Page 266
Myelodysplasia......Page 269
Myeloid leukemia......Page 270
AIDS......Page 271
Comment......Page 272
15 - Conclusions......Page 276
References......Page 283
Index......Page 343