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INTRODUCTION

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SUMMARY

The neutrophil circulates in blood as a quiescent cell. Its main function as a phagocytic and bactericidal cell is performed outside the circulation in tissues where microbial invasion takes place. Neutrophil function is traditionally viewed as chemotaxis, phagocytosis, and bacterial killing. Although these conceptionally represent distinct entities, they are functionally related, and rely to a large extent on the same intracellular signal transduction mechanisms that result in localized rises in intracellular Ca2+, changes in organization of the cytoskeleton, assembly of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase from its cytosolic and membrane integrated subunits, and fusion of granules with the phagosome or neutrophil plasma membrane. Clinical disorders of the neutrophil may arise from impairment of these normal functions. The clinical presentation of a patient who has a qualitative neutrophil abnormality may be similar to that of one who has an antibody, complement, or toll-like receptor disorder. In general, evaluation for phagocyte cell disorders should be initiated among those patients who have at least one of the following clinical features: (1) two or more systemic bacterial infections in a relatively short time period; (2) frequent, serious respiratory infections, such as pneumonia or sinusitis, or otitis media, or lymphadenitis; (3) infections present at unusual sites (liver or brain abscess); and (4) infections associated with unusual pathogens (e.g., Aspergillus pneumonia, disseminated candidiasis, or infections with Serratia marcescens, Nocardia species, or Burkholderia cepacia).

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Acronyms and Abbreviations

ADP, adenosine diphosphate; ARF, ADP-ribosylation factor; ASC, apoptosis-associated speck-like protein with a caspase recruitment domain; ATPase, adenosine triphosphatase; BPI, bacterial permeability-increasing protein; cAMP, cyclic adenosine monophosphate; cANCA, cytoplasmic antineutrophil cytoplasmic antibody; CARD, caspase activation and recruitment domain; c/EBP, CCAAT/enhancer binding protein; CGD, chronic granulomatous disease; CHS, Chédiak-Higashi syndrome; DAG, diacylglycerol; DOCK8, dedicator of cytokinesis 8; ESAM, endothelial cell-selective adhesion molecule; FAD, flavin adenine dinucleotide; FMF, familial Mediterranean fever; fMLP, formyl-methionyl-leucyl-phenylalanine; G6PD, glucose-6-phosphate dehydrogenase; GDP, glucose diphosphate; GPI, glycosylphosphatidylinositol; GTP, guanosine triphosphate; GTPase, guanosine triphosphatase; H2O2, hydrogen peroxide; HBP, heparin-binding protein; HETE, hydroxyeicosatetraenoic acid; HLA, human leukocyte antigen; HNP, human neutrophil peptide (synonym: defensin); ICAM, intercellular adhesion molecule; IFN, interferon; Ig, immunoglobulin; IL, interleukin; IP3, inositol triphosphate; ITAM, immunoreceptor tyrosine-based activation motif; JAMs, junctional adhesion molecule A, B, and C; LAD, leukocyte adhesion deficiency; LFA-1, leukocyte function-associated antigen-1; LPS, lipopolysaccharide; LSP-1, lymphocyte-specific protein-1; LTB4, leukotriene B4; Mal/TIRAP, MyD88-adaptor-like/toll/interleukin-1 receptor domain containing adaptor protein; MAPK, microtubule-associated protein kinase; MBL, mannose-binding lectin; MMP, matrix metalloproteinase; MPO, myeloperoxidase; MyD88, myeloid differentiation factor 88; NADPH, nicotinamide adenine dinucleotide phosphate (reduced form); NBT, nitroblue tetrazolium; NEM, N-ethylmaleimide; NET, neutrophil extracellular trap; NF-κB, nuclear factor-κB; NGAL, neutrophil gelatinase-associated lipocalin; NK, natural killer; NSF, N-ethylmaleimide–sensitive fusion protein; NSP4, neutrophil serine protease 4; PA, phosphatidic acid; PAF, platelet-activating factor; PECAM, platelet endothelial adhesion molecule; phox, phagocyte oxidase; PI3K, phosphatidylinositol 3′-kinase; PIP1, phosphatidylinositol-4-monophosphate; PIP2, phosphatidylinositol-4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; ...

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