Contents -- Preface -- List of Contributors -- Chapter 1: Molecular Regulation of Granulopoiesis Sachin Kumar and Marie-Dominique Filippi -- 1.1 Introduction -- 1.2 Sequential Steps of PMN Development -- 1.2.1 From HSC to granulocytic precursors -- 1.2.2 Final stages of granulocytic maturation - Acquisition of granulocyte characteristics -- 1.3 Regulation of Steady State Granulopoiesis -- 1.3.1 Growth factors -- 1.3.1.1 G-CSF: Sources and functions -- 1.3.1.2 G-CSFR and downstream signaling pathways -- 1.3.1.3 G-CSFR signaling: Instructive or permissive? -- 1.3.2 Transcription factors (TF) -- 1.3.2.1 PU.1 - Generation of CMP from HSC -- 1.3.2.2 C/EBPα - Generation of GMP from CMP -- 1.3.2.3 C/EBPε - Terminal stages of differentiation -- 1.3.2.4 Gfi-1 - Terminal stages of differentiation -- 1.3.2.5 Other transcription factors important for granulopoiesis -- 1.3.2.5.1 Retinoic acid receptors -- 1.3.2.5.2 HoxA10 -- 1.3.2.5.3 LEF-1 -- 1.3.3 MicroRNA -- 1.3.4 Cell cycle regulation -- 1.4 Emergency Granulopoiesis -- 1.5 Conclusion -- References -- Chapter 2: The Neutrophil Respiratory Burst Oxidase Mark T. Quinn -- 2.1 Introduction -- 2.2 NADPH Oxidase Components -- 2.2.1 Flavocytochrome b -- 2.2.2 p47phox -- 2.2.3 p67phox -- 2.2.4 p40phox -- 2.2.5 Rac -- 2.2.6 Rap1A -- 2.3 Oxidase Protein Binding Interactions -- 2.3.1 Flavocytochrome b-p47phox interactions -- 2.3.2 p40phox-p47phox-p67phox interactions -- 2.3.3 Rac interactions -- 2.4 Model of NADPH Oxidase Assembly -- 2.5 Oxidant Production -- 2.5.1 Superoxide anion (O2 -) -- 2.5.2 Hydrogen peroxide (H2O2) -- 2.5.3 Hypochlorous acid (HOCl) -- 2.5.4 Hydroxyl radical (HO) -- 2.5.5 Singlet oxygen ( 1O2 *) -- 2.5.6 Nitric oxide (NO) and peroxynitrite (ONOO-) -- 2.7 Summary -- Acknowledgments -- References.

Chapter 3: Novel Neutrophil Receptors and Their Signal Transduction Nicole R. Fortenbery, Xianhong Chen and Sheng Wei -- 3.1 Introduction -- 3.2 Siglecs -- 3.2.1 Identification of siglecs -- 3.2.2 Characterization of siglecs -- 3.2.3 Siglec-5 -- 3.2.4 Siglec-9 -- 3.2.5 Siglec-14 -- 3.2.6 Siglec signaling -- 3.2.7 Clinical applications -- 3.3 Triggering Receptor Expressed by Myeloid Cells (TREM) -- 3.3.1 Identification of TREM -- 3.3.2 Characterization of TREM-1 -- 3.3.3 TREM-1-DAP12 and signal transduction -- 3.3.4 TREM-1 ligand(s) -- References -- Chapter 4 Mechanisms of Neutrophil Migration Fong W. Lam, Rolando E. Rumbaut and Alan R. Burns -- 4.1 Introduction -- 4.2 Historical Perspective on Leukocyte Adhesion and Emigration (1669-1955) -- 4.2.1 The first observations -- 4.2.2 Mechanistic insight -- 4.3 Molecular Adhesive Events Preceding Neutrophil Transendothelial Migration -- 4.4 Integrin Regulation of Neutrophil Transendothelial Migration -- 4.5 Paracellular Neutrophil Transendothelial Migration -- 4.5.1 Endothelial cleft organization -- 4.5.2 Tight junctions and preferred transmigration sites -- 4.5.3 Adherens junctions -- 4.5.4 Gap junctions -- 4.5.5 PECAM-1 -- 4.5.6 CD99 -- 4.5.7 Junctional adhesion molecules (JAM) -- 4.5.8 JAM-A -- 4.5.9 JAM-B and JAM-C -- 4.6 Transcellular Neutrophil Transendothelial Migration -- 4.7 Endothelial Permeability Responses to Neutrophil Transendothelial Migration -- 4.8 The Role of Platelets in Neutrophil Transmigration -- 4.9 Concluding Remarks -- Acknowledgments -- References -- Chapter 5 Cytokine Production by Neutrophils Luc de Chaisemartin, Marco Cassatella and Sylvie Chollet-Martin -- 5.1 Introduction -- 5.2 General Features of Cytokine Production by Human Neutrophils -- 5.3 Production of Specific Cytokines by Neutrophils -- 5.3.1 Chemokines -- 5.3.1.1 IL-8/CXCL8 and GROα/CXCL1.

5.3.1.2 IFN-γ-inducible protein of 10 kDa (IP-10/CXCL10) -- 5.3.1.3 Macrophage inflammatory protein-1α and β (MIP-1α/CCL3 and MIP-1β/CCL4) -- 5.3.2 Proinflammatory cytokines -- 5.3.2.1 Tumor Necrosis Factor-α (TNF-α) -- 5.3.2.2 Interleukin-1 -- 5.3.2.3 Interleukin-6 -- 5.3.2.4 Interleukin-12 -- 5.3.2.5 Interferon (IFN)-α -- 5.3.2.6 Interferon-γ (IFN-γ) -- 5.3.2.7 IL-17 -- 5.3.3 Anti-inflammatory cytokines -- 5.3.3.1 Interleukin-4 -- 5.3.3.2 Transforming growth factor -- 5.3.3.3 IL-10 -- 5.3.4 Cytokine inhibitors -- 5.3.4.1 Oncostatin M (OSM) -- 5.3.5 Growth factors -- 5.3.5.1 Hepatocyte growth factor (HGF) -- 5.3.5.2 Vascular endothelial growth factor (VEGF) -- 5.3.5.3 Colony-stimulating factors (CSF) -- 5.4 Cross-Talk with Other Cells -- 5.5 Patterns of Cytokine Production in Human Neutrophils -- 5.5.1 Degranulation -- 5.5.2 De novo protein synthesis -- 5.5.3 Shedding of membrane-bound cytokine -- 5.5.4 Expression of receptor-bound cytokine -- 5.5.5 Neutrophil extracellular traps (NET)-associated release -- 5.5.6 Modulation of PMN-derived cytokine release using various mechanisms -- 5.5.7 Cellular models of neutrophil cytokine production -- 5.6 Conclusion -- References -- Chapter 6: Neutrophils and Apoptosis Christopher D. Lucas and Adriano G. Rossi -- 6.1 Introduction -- 6.2 Apoptosis -- 6.2.1 Caspases -- 6.2.2 Intrinsic pathway of apoptosis -- 6.2.3 Extrinsic pathway of apoptosis -- 6.3 Neutrophil Lifespan Under Basal and Inflammatory Conditions -- 6.4 Signalling Pathways Controlling Neutrophil Apoptosis -- 6.5 Recognition and Clearance of Apoptotic Neutrophils -- 6.6 Neutrophil Apoptosis and the Resolution of Inflammation -- 6.7 Conclusions and Future Directions of Apoptosis Research -- References -- Chapter 7 Regulation of Neutrophil Functions by Long Chain Fatty Acids Antonio Ferrante, Charles S. Hii and Bernadette Boog -- 7.1 Introduction.

7.2 Fatty Acids -- 7.2.1 Sources, uptake and receptors of fatty acids -- 7.2.2 Release of fatty acids during cell activation - role of phospholipase A2 -- 7.3 Metabolism of Arachidonic Acid and Other Fatty Acids -- 7.3.1 General -- 7.3.2 Metabolism in neutrophils -- 7.3.2.1 Acylation into phospholipids and triglycerides -- 7.3.2.2 5-lipoxygenase -- 7.3.2.3 12-lipoxygenase -- 7.3.2.4 15-lipoxygenase -- 7.3.2.5 Cyclooxygenase -- 7.3.2.6 ω-oxidation -- 7.3.3 Transcellular metabolism -- 7.3.3.1 Lipoxins -- 7.3.3.2 Resolvins and protectins -- 7.4 Biological Properties of AA -- 7.4.1 Effects on neutrophil adhesion, cell migration and chemotaxis -- 7.4.2 Activation of the NADPH oxidase -- 7.4.3 Stimulation of degranulation -- 7.5 Effects of n-3 Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acid on Neutrophils -- 7.6 Regulation of Neutrophil Functions by Metabolites of AA -- 7.6.1 Products of the lipoxygenase pathway -- 7.6.2 Products of the cyclooxygenase pathway -- 7.6.3 Hydroxynonenal, a peroxidation product of AA -- 7.7 Biological Properties of Resolvins and Protectins -- 7.8 Relationship Between Fatty Acid Structure and Biological Function -- 7.9 Cytokine-Induced Alteration in Neutrophil Responses to Polyunsaturated Fatty Acids -- 7.10 Neutrophil Priming Properties of Fatty Acids -- 7.10.1 Alteration of responses to fMLF and PMA -- 7.10.2 Antimicrobial activity -- 7.10.3 Tissue damage -- 7.10.4 Cell surface receptor expression -- 7.11 Mechanisms of Fatty Acid-Induced Neutrophil Activation -- 7.11.1 Polyunsaturated fatty acids stimulate neutrophils independently of lipoxygenase and cyclooxygenase pathways -- 7.11.2 Differences in metabolism of long chain and very long chain polyunsaturated fatty acids -- 7.11.3 Activation of intracellular signals -- 7.11.3.1 Mobilisation of intracellular calcium -- 7.11.3.2 Heterotrimeric G proteins.

7.11.3.3 Protein kinase C (PKC) -- 7.11.3.4 Activation of PLA2 by 20:4n-6 and other fatty acids -- 7.11.3.5 Activation of the MAP kinases -- 7.11.3.6 Activation of sphingomyelinase -- 7.11.3.7 Phosphatidylinositol 3-kinase (PI3K) -- 7.11.3.8 Ion channels -- 7.11.3.9 Modulation of the activation status of small GTP-binding proteins -- 7.11.4 Evidence for an involvement of PKC, ERK, p38 and PI3K in AA-stimulated superoxide production -- 7.11.5 Involvement of ERK1/ERK2 and p38 in regulating 5-LOX -- 7.11.6 Interaction between AA and S100 proteins in regulation of NADPH oxidase activation -- 7.12 Modulation of TNF Receptor Expression -- 7.13 Novel Polyunsaturated Fatty Acids -- 7.14 Summary -- Acknowledgments -- References -- Chapter 8 S100 Calgranulins in Inflammation Carolyn L. Geczy, Phillipe A. Tessier and Lincoln Gomes -- 8.1 S100s in Neutrophils -- 8.2 Calgranulin Structure -- 8.3 Disease Associations -- 8.4 Mechanisms of Secretion -- 8.5 Intracellular Functions -- 8.5.1 Gene expression, cell growth, and differentiation -- 8.5.2 Cytoskeletal organization -- 8.5.3 Fatty acid and arachidonic acid transport -- 8.5.4 NADPH oxidase assembly and activation -- 8.5.5 S100A12 -- 8.6 Extracellular Functions -- 8.6.1 Putative calgranulin receptors -- 8.6.2 Chemotaxis, adhesion and migration -- 8.6.3 Activation of cells -- 8.6.4 Antimicrobial and anti-invasive properties -- 8.6.5 Regulation of matrix metalloproteinases (MMP) -- 8.6.6 Apoptosis -- 8.7 Functions Learnt from Murine Models -- 8.7.1 Gene deletion of S100A8 and S100A9 -- 8.7.2 S100A9-/- models -- 8.8 Oxidant Scavenging by S100A8 and S100A9 -- 8.8.1 Structural modifications generated by oxidation and functional consequences -- 8.8.1.1 Oxidation by hypohalous acids -- 8.8.1.2 Some functional consequences of oxidation -- 8.8.2 S-nitrosylation -- 8.8.3 S-glutathionylation -- 8.9 Summary.

Acknowledgments.