The Neutrophils: New Outlook For Old Cells

by Gabrilovich, Dmitry I.

• ISBN13: 9781860944727
• ISBN10: 1860944728
• Edition: 2nd
• Format: Hardcover
• Copyright: 2005-04-01
• Publisher: World Scientific Pub Co Inc

Summary

- A unique review of neutrophil signaling, and the role of rac 1 and rac 2 in neutrophil function- The role of fatty acids in neutrophil function -- information not available in other books- The role of neutrophils in viral infections -- usually beyond the radar screen of investigators- The role of neutrophil function in cancer -- a topic of recent, great interest to many research groups

Table of Contents

Preface	xvii
Contributors	xxi
1 The Remarkable Neutrophil! Developing a Blueprint for Integrated Cellular Signaling	1	(34)
1. Introduction	2	(2)
1.1. Second messengers	3	(1)
1.2. Integrated cellular signaling	3	(1)
2. The life of the neutrophil	4	(15)
2.1. Bone marrow origin of the neutrophil	4	(2)
2.2. The fate of circulating neutrophils	6	(1)
2.3. Neutrophil stimulators	6	(4)
2.3.1. Do diverse biochemical events underlie stimulation?	7	(1)
2.3.2. Functional maturation	8	(2)
2.4. Neutrophil adherence	10	(2)
2.4.1. Biophysical aspects of adherence	11	(1)
2.4.2. Integrins	12	(1)
2.5. Chemotaxis	12	(3)
2.5.1. Rho family GTPases	13	(1)
2.5.2. Rho-kinase	13	(2)
2.6. Neutrophil priming	15	(1)
2.7. The respiratory burst: free radicals in biology	15	(3)
2.7.1. The enzyme involved	16	(1)
2.7.2. Back to Rac	17	(1)
2.8. Neutrophil-endothelial cell communication	18	(1)
3. Integrated cellular signaling	19	(1)
4. Molecular mechanisms of cellular activation	20	(9)
4.1. Protein phosphorylation in cellular activation	23	(3)
4.2. The Rac/Rho equilibrium, revisited	26	(3)
5. A unifying hypothesis	29	(1)
6. Conclusions	30	(1)
References	31	(4)
2 The Neutrophil Respiratory Burst Oxidase	35	(50)
1. Introduction	36	(1)
2. NADPH oxidase components	37	(19)
2.1. Flavocytochrome b	38	(6)
2.2. p47phox	44	(4)
2.3. p67phox	48	(4)
2.4. p40phox	52	(2)
2.5. Rac	54	(1)
2.6. Rap1A	55	(1)
3. Oxidase protein binding interactions	56	(7)
3.1. Flavocytochrome b-p47phox interactions	56	(3)
3.2. p40phox-p47phox-p67phox interactions	59	(2)
3.3. Rac interactions	61	(2)
4. Model of NADPH oxidase assembly	63	(3)
5. Oxidant production	66	(6)
5.1. Superoxide anion (O2-)	66	(1)
5.2. Hydrogen peroxide (H2O2)	67	(1)
5.3. Hypochlorous acid (HOCl)	68	(1)
5.4. Hydroxyl radical (HO)	68	(2)
5.5. Singlet oxygen (¹O2*) and ozone (O3)	70	(1)
5.6. Nitric oxide (NO) and peroxynitrite (ONOO-)	70	(2)
6. Summary	72	(1)
Acknowledgments	72	(1)
References	73	(12)
3 Novel Neutrophil Receptors and Their Signal Transduction	85	(20)
1. Introduction	86	(1)
2. Triggering receptor expressed by myeloid cells (TREM)	87	(4)
2.1. Identification of TREMs	88	(1)
2.2. Characterization of TREM1	88	(1)
2.3. DAP12 and its signal transduction	89	(1)
2.4. TREM1 ligand(s)	90	(1)
2.5. Biological function of TREM1	90	(1)
3. Toll-like receptor (TLR)	91	(5)
3.1. Expression of TLRs in neutrophils	91	(1)
3.2. Biologic function of TLRs	92	(3)
3.3. TLR signal transduction pathways	95	(1)
3.3.1. MyD88 dependent pathway	95	(1)
3.3.2. MyD88 independent pathway	95	(1)
4. The Fc receptors (FcR)	96	(5)
4.1. Activation and inhibition of FcR	97	(1)
4.2. FcR-mediated signaling in neutrophils	98	(3)
References	101	(4)
4 Mechanisms of Neutrophil Migration	105	(48)
1. Introduction	106	(1)
2. Historical perspective on leukocyte adhesion and emigration (1669-1955)	107	(3)
2.1. The first observations	107	(1)
2.2. Mechanistic insight	108	(2)
3. Molecular adhesive events preceding neutrophil transendothelial migration	110	(2)
4. Integrin regulation of neutrophil transendothelial migration	112	(2)
5. Paracellular neutrophil transendothelial migration	114	(14)
5.1. Endothelial cleft organization	114	(1)
5.2. Tight junctions and preferred transmigration sites	115	(5)
5.3. Adherens junctions	120	(2)
5.4. Gap junctions	122	(1)
5.5. PECAM-1	123	(2)
5.6. CD99	125	(1)
5.7. JAMs	126	(1)
5.8. JAM-A	127	(1)
5.9. JAM-B and JAM-C	128	(1)
6. Transcytotic neutrophil and transendothelial migration	128	(4)
7. Endothelial permeability responses to neutrophil transendothelial migration	132	(8)
8. Concluding remarks	140	(1)
Acknowledgments	141	(1)
References	141	(12)
5 Neutrophils and Apoptosis	153	(16)
1. Introduction	154	(1)
2. Neutrophil apoptosis	154	(2)
3. Regulation of neutrophil apoptosis	156	(7)
3.1. Internal control mechanisms	156	(5)
3.1.1. Caspases	156	(2)
3.1.2. Initiation of apoptosis	158	(2)
3.1.3. Mitochondria and Bcl-2 family proteins	160	(1)
3.2. Regulation of neutrophil apoptosis by external mediators	161	(2)
4. Clearance of apoptotic neutrophils	163	(1)
5. Concluding remarks	164	(1)
References	165	(4)
6 Regulation of Neutrophil Functions by Long Chain Fatty Acids	169	(60)
1. Introduction	170	(1)
2. Fatty acids	171	(4)
2.1. De novo synthesis	172	(1)
2.2. Diet	172	(1)
2.3. Phospholipase A2	173	(2)
3. Transport and uptake of fatty acids	175	(1)
4. Metabolism of arachidonic acid and other fatty acids	176	(7)
4.1. General	176	(2)
4.2. Metabolism in neutrophils	178	(6)
4.2.1. Acylation into phospholipids and triglycerides	178	(2)
4.2.2. 5-lipoxygenase	180	(1)
4.2.3. 12-lipoxygenase	181	(1)
4.2.4. 15-lipoxygenase	182	(1)
4.2.5. Cyclooxygenase	182	(1)
4.2.6. ω-oxidation	183	(1)
5. Transcellular metabolism	183	(1)
6. Biological properties of arachidonic acid	184	(2)
6.1. Effects on neutrophil adhesion, cell migration and chemotaxis	184	(1)
6.2. Activation of the NADPH oxidase	185	(1)
6.3. Stimulation of degranulation	186	(1)
7. Effects of n-3 fatty acids, eicosapentaenoic and docosahexaenoic acid on neutrophils	186	(1)
8. Regulation of neutrophil functions by metabolites of arachidonic acid	187	(3)
8.1. Products of the lipoxygenase pathway	188	(1)
8.2. Products of the cyclooxygenase pathway	189	(1)
9. Relationship between fatty acid structure and biological function	190	(3)
10. Cytokine induced alteration in neutrophil responses to polyunsaturated fatty acids	193	(1)
11. Neutrophil priming properties of fatty acids	194	(5)
11.1. Alteration of responses to fMLP and PMA	195	(1)
11.2. Antimicrobial activity	195	(1)
11.3. Tissue damage	196	(1)
11.4. Cell surface receptor expression	197	(2)
12. Mechanisms of fatty acid-induced neutrophil activation	199	(14)
12.1. Polyunsaturated fatty acids stimulate neutrophils independently of lipoxygenase and cyclooxygenase pathways	199	(1)
12.2. Differences in metabolism of long chain and very long chain polyunsaturated fatty acids	200	(1)
12.3. Activation of intracellular signals	201	(9)
12.3.1. Mobilization of intracellular calcium	201	(2)
12.3.2. Heterotrimeric G-proteins	203	(1)
12.3.3. Protein kinase C	204	(1)
12.3.4. Activation of PLA2 by 20:4n-6 and other fatty acids	204	(2)
12.3.5. Activation of the MAP kinases	206	(1)
12.3.6. Activation of sphingomyelinase	207	(1)
12.3.7. Phosphatidylinositol 3-kinase	207	(2)
12.3.8. Ion channels	209	(1)
12.3.9. Modulation of the activation status of small GTP binding proteins	209	(1)
12.4. Evidence for an involvement of PKC, ERK, p38 and PI3K in AA-stimulated superoxide production	210	(3)
12.5. Involvement of ERK1/ERK2 and p38 in regulating 5-LOX	213	(1)
13. Modulation of TNFR expression	213	(1)
14. Novel polyunsaturated fatty acids	214	(1)
15. Summary	215	(3)
Acknowledgments	218	(1)
References	218	(11)
7 Cytokine Production by Neutrophils	229	(24)
1. Introduction	229	(1)
2. General features of cytokine production by human neutrophils	230	(1)
3. Production of specific cytokines by neutrophils	231	(11)
3.1. Chemokines	231	(3)
3.2. Proinflammatory cytokines	234	(3)
3.3. Anti-inflammatory cytokines	237	(2)
3.4. Cytokine inhibitors	239	(1)
3.5. Growth factors	240	(2)
4. Cross-talk with others cells	242	(1)
5. Patterns of cytokines production in human neutrophils	243	(5)
5.1. Degranulation	243	(2)
5.2. De novo protein synthesis	245	(1)
5.3. Shedding of membrane-bound cytokine	246	(1)
5.4. Expression of receptor-bound cytokine	246	(1)
5.5. Modulation of PMN-derived cytokine release using various mechanisms	247	(1)
6. Conclusion	248	(1)
References	249	(4)
8 Neutrophils in Viral Infections	253	(22)
1. Introduction	253	(2)
2. Inhibition of viruses by neutrophils	255	(2)
2.1. Viral inactivation by oxygen intermediates	256	(1)
2.2. Antibody and complement induced viral inactivation	257	(1)
3. Activation of neutrophils by viruses	257	(3)
3.1. Activation by binding of virus	258	(1)
3.2. Adherence of neutrophils to infected cells	259	(1)
3.3. Activation of oxidative burst activity	259	(1)
3.4. Role of cytokines in neutrophil activation	259	(1)
4. Neutrophil functions inhibited by viruses	260	(1)
5. Neutrophils and influenza A virus	261	(2)
6. Neutrophils and HIV	263	(5)
6.1. Myelodysplastic changes in HIV infection	264	(1)
6.2. HIV infection of neutrophils	264	(1)
6.3. Anti-neutrophil antibodies in HIV infection	265	(1)
6.4. Neutrophil chemotaxis in HIV infection	265	(1)
6.5. Abnormalities in respiratory burst activity	266	(1)
6.6. Neutrophil cytotoxicity in HIV infection	267	(1)
6.7. Neutrophil defensins inhibit HIV	268	(1)
7. Conclusion	268	(1)
References	269	(6)
9 Polymorphonuclear Neutrophils and Cancer: Ambivalent Role in Host Defense Against Tumor	275	(26)
1. Neutrophils are able to promote carcinogenesis	276	(7)
1.1. PMNs may contribute to inflammation associated with tumor development	276	(1)
1.2. PMNs involvement in infection associated carcinogenesis	277	(2)
1.3. Myeloperoxidase and cancer	279	(1)
1.4. Chemokines regulate neutrophil infiltration and activity	280	(1)
1.5. PMNs can promote tumor metastases	281	(2)
2. The role of neutrophils in antitumor reactions	283	(9)
2.1. PMN-mediated tumor destruction	283	(3)
2.2. Cytokine and chemokine-induced PMN anti-tumor activity	286	(4)
2.3. Neutrophils as effectors of antibody-dependent cell-mediated cytotoxicity against tumor	290	(2)
3. Conclusion	292	(2)
References	294	(7)
10 Use of Colony-Stimulating Factors for Treatment of Neutropenia and Infectious Diseases	301	(26)
1. Characteristics of G-CSF, GM-CSF and its receptors	302	(1)
2. Neutrophil and monocyte development and function	303	(5)
3. Measurement of CSF levels in patients with neutropenia and infectious diseases	308	(2)
4. G-CSF in nonneutropenic animal models of infection	310	(8)
4.1. Neonatal sepsis	311	(1)
4.2. Burn wound injury	312	(1)
4.3. Surgical wound infection	312	(1)
4.4. Bacteremia	313	(2)
4.5. Intraabdominal infection	315	(1)
4.6. Pneumonia	315	(3)
5. Clinical studies of the CSFs in infectious diseases	318	(4)
5.1. Neutropenia	318	(1)
5.2. G-CSF in nonneutropenic patients with pneumonia	319	(3)
References	322	(5)
11 Neutrophil Transfusion Therapy in the G-CSF Era	327	(22)
1. Introduction	327	(2)
2. Therapeutic neutrophil transfusions	329	(8)
2.1. Historic experience with therapeutic PMN transfusions in neutropenic patients	329	(2)
2.2. Modern experience with therapeutic PMN transfusions in the G-CSF era	331	(6)
2.3. Therapeutic PMN transfusions for neonatal sepsis	337	(1)
3. Prophylactic neutrophil transfusions	337	(2)
3.1. Historic experience with prophylactic transfusions in neutropenic patients	337	(1)
3.2. Modern experience with prophylactic PMN transfusions in neutropenic patients	338	(1)
4. Methods for PMN collection and transfusion	339	(5)
4.1. Preleukapheresis donor stimulation	339	(1)
4.2. Leukapheresis techniques	340	(1)
4.3. Erythrocyte sedimenting agents	341	(2)
4.4. Transfusion of PMN concentrates	343	(1)
Acknowledgments	344	(1)
References	344	(5)
Index	349