Chapter 061. Disorders of Granulocytes and Monocytes (Part 3)

Pelger-Hüet anomaly. In this benign disorder, the majority of granulocytes are bilobed. The nucleus frequently has a spectacle-like, or "pince-nez," configuration.In severe acute bacterial infection, prominent neutrophil cytoplasmic granules, called toxic granulations, are occasionally seen. Toxic granulations are immature or abnormally staining azurophil granules. Cytoplasmic inclusions, also called Döhle bodies (Fig. 61-3), can be seen during infection and are fragments of ribosome-rich endoplasmic reticulum. Large neutrophil vacuoles are often present in acute bacterial infection and probably represent pinocytosed (internalized) membrane.Neutrophils are heterogeneous in function. Monoclonal antibodies have been developed that recognize only a subset of mature neutrophils. The meaning...
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Chapter 061. Disorders of Granulocytes and Monocytes (Part 3) Chapter 061. Disorders of Granulocytes and Monocytes (Part 3) Pelger-Hüet anomaly. In this benign disorder, the majority of granulocytesare bilobed. The nucleus frequently has a spectacle-like, or pince-nez,configuration. In severe acute bacterial infection, prominent neutrophil cytoplasmicgranules, called toxic granulations, are occasionally seen. Toxic granulations areimmature or abnormally staining azurophil granules. Cytoplasmic inclusions, alsocalled Döhle bodies (Fig. 61-3), can be seen during infection and are fragments ofribosome-rich endoplasmic reticulum. Large neutrophil vacuoles are often presentin acute bacterial infection and probably represent pinocytosed (internalized)membrane. Neutrophils are heterogeneous in function. Monoclonal antibodies havebeen developed that recognize only a subset of mature neutrophils. The meaningof neutrophilheterogeneity is not known. The morphology of eosinophils and basophils is shown in Fig. 61-6. Figure 61-6 Normal eosinophil and basophil. The eosinophil contains large, brightorange granules and usually a bilobed nucleus. The basophil contains large purple-black granules that fill the cell and obscure the nucleus Marrow Release and Circulating Compartments Specific signals, including IL-1, tumor necrosis factor α (TNF-α), the CSFs,complement fragments, and chemokines, mobilize leukocytes from the bonemarrow and deliver them to the blood in an unstimulated state. Under normalconditions, ~90% of the neutrophil pool is in the bone marrow, 2–3% in thecirculation, and the remainder in the tissues (Fig. 61-7). Figure 61-7 Schematic neutrophil distribution and kinetics between the differentanatomic and functional pools The circulating pool exists in two dynamic compartments: one freelyflowing and one marginated. The freely flowing pool is about one-half theneutrophils in the basal state and is composed of those cells that are in the bloodand not in contact with the endothelium. Marginated leukocytes are those that arein close physical contact with the endothelium (Fig. 61-8). In the pulmonarycirculation, where an extensive capillary bed (~1000 capillaries per alveolus)exists, margination occurs because the capillaries are about the same size as amature neutrophil. Therefore, neutrophil fluidity and deformability are necessaryto make the transit through the pulmonary bed. Increased neutrophil rigidity anddecreased deformability lead to augmented neutrophil trapping and margination inthe lung. In contrast, in the systemic postcapillary venules, margination ismediated by the interaction of specific cell-surface molecules called selectins.Selectins are glycoproteins expressed on neutrophils and endothelial cells, amongothers, that cause a low-affinity interaction, resulting in rolling of the neutrophilalong the endothelial surface. On neutrophils, the molecule L-selectin [clusterdeterminant (CD) 62L] binds to glycosylated proteins on endothelial cells [e.g.,glycosylation-dependent cell adhesion molecule (GlyCAM1) and CD34].Glycoproteins on neutrophils, most importantly sialyl-Lewisx (SLex, CD15s), aretargets for binding of selectins expressed on endothelial cells [E-selectin (CD62E)and P-selectin (CD62P)] and other leukocytes. In response to chemotactic stimulifrom injured tissues (e.g., complement product C5a, leukotriene B 4, IL-8) orbacterial products [e.g., N-formylmethionylleucylphenylalanine (f-metleuphe)],neutrophil adhesiveness increases, and the cells stick to the endothelium throughintegrins. The integrins are leukocyte glycoproteins that exist as complexes of acommon CD18 βchain with CD11a (LFA-1), CD11b (called Mac-1, CR3, or theC3bi receptor), and CD11c (called p150, 95 or CR4). CD11a/CD18 andCD11b/CD18 bind to specific endothelial receptors [intercellular adhesionmolecules (ICAM) 1 and 2].