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940 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 61: Production, Distribution, and Fate of Neutrophils 941

TABLE 61–1. Marrow Neutrophil Kinetics
Fraction in Mitosis Fraction in DNA Transit Time
(Mitotic Index) Synthesis (S Phase) Range (h) Total Cells (× 0 /kg)
9
Mitotic compartment
Myeloblast 0.025 0.85 23 0.14
Promyelocyte 0.015 0.65 26–78 0.51
Myelocyte 0.011 0.33 17–126 1.95
Maturation storage compartment
Metamyelocyte 8–108 2.7
Band 12–96 3.6
Polymorphonuclear neutrophil 0–120 2.5

calculated normal marrow neutrophil production of 0.85 × 10 cells/ are temporarily sequestered in the alveolar capillaries of the lung (the
9
kg per day. Radioautographic studies with [ H]thymidine support the marginated pool). 55,56 Cells in the two pools are freely exchangeable.
3
concept of an orderly progression from metamyelocytes to mature When neutrophils labeled with DF P are injected into normal sub-
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neutrophils within the maturation storage compartment. These studies jects, approximately half can be accounted for in the circulating pool;
also suggest a “first in, first out” pattern for cells leaving this compart- the remainder enters the marginated pool. Neutrophils shift from the
5–7
ment and entering the blood. Several labeling techniques indicate the marginated to the circulating pool with exercise, epinephrine injection,
myelocyte-to-blood transit time is 5 to 7 days. 12,50 Previous studies with or stress, but eventually the neutrophils leave the blood and enter the
DF P reported a range from 8 to 14 days. During infections, how- tissues. Once the neutrophils enter the tissues, they do not normally
9,49
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ever, the myelocyte-to-blood transit time may be as short as 48 hours. 51 return to the blood. The flow of cells is unidirectional.
Whether the production of neutrophils in the mitotic compart- DF P-labeled neutrophils disappear from the circulation with a
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ment exactly equals the neutrophil turnover rate (NTR) is not known half-time (T ) of 6.7 hours. 7,57,58 These data are supported by the find-
1/2
with certainty. Studies in dogs suggest some immature neutrophils ing that more than half of Pelger-Huët cells infused into a normal indi-
die in the marrow (“ineffective granulopoiesis”). Ineffective gran- vidual disappeared after 6 to 8 hours. Data obtained with Cr-labeled
51
59
52
ulopoiesis has not been shown in normal humans, 14,53 although inef- neutrophils give substantially longer half-times. The exponential dis-
60
fective granulopoiesis occurs in some pathologic states, including the appearance of cells from the blood suggests the cells leave in a random
myelodysplastic syndromes, myelofibrosis, and some of the idiopathic manner. Thus, neutrophils newly released from the marrow are as likely
54
neutropenic disorders. At present, however, no convenient means of to leave the blood as are neutrophils that have been circulating for sev-
quantitating ineffective granulopoiesis is available. eral hours. Neutrophils also are eliminated by programmed cell death
On completion of maturation, the neutrophils are stored in the and disposed of by the macrophage system. 51,61–64
marrow and are referred to as the mature neutrophil reserve. The reserve Direct observations of blood vessels have revealed some degree
contains many more cells than are normally circulating in the blood. of leukocyte rolling along the endothelium (first observed many years
Table 61–2 lists comparative data on the characteristics of the matura- ago by Atherton and Born ). Although the observation has been clearly
60
tion storage compartment. Under stress, maturation time may be short- confirmed by numerous laboratories in different species of animals, the
ened, divisions may be skipped, and release into the blood may occur extent to which this phenomenon contributes to the marginated pool of
prematurely. neutrophils is uncertain.
A more compelling concept of the marginated pool is derived
The Blood from investigations of the vascular bed of the lung. A distinctive
Neutrophils leave the marrow storage compartment and enter the characteristic of this tissue is the complex interconnecting network
blood without significant reentry into the marrow. The total blood of short capillary segments where the path from arteriole to venule
neutrophil pool (TBNP) consists of all the neutrophils in the vascular crosses several alveolar walls (often more than eight) and often con-
spaces. Some of these neutrophils are free in the circulation (the circu- tains more than 50 capillary segments. 65–69 Compared to blood in the
lating pool), while others roll along the endothelium of small vessels or large vessels of most vascular beds, the blood in this complex network

TABLE 61–2. Comparative Data on Marrow Maturation Storage Compartment
Size (Cells × 10 kg) Transit Time (Days) Measurement Technique Reference
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6.5–13 4–8 [ H]thymidine, in vitro DF P 5
3
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3–23 8–14 In vivo and in vitro DF P 45
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5.6 6.6 59 Fe and neutrophil/erythroid ratio 14
DF P, diisopropyl fluorophosphate.
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Kaushansky_chapter 61_p0939-0946.indd 941 9/18/15 9:41 AM