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CHAPTER 70 and has greater tumoricidal activity; the larger population represents a
more-mature stage, has a lower buoyant density, has a larger cell vol-
MONOCYTOSIS AND ume, displays Fc receptors, expresses more peroxidase activity, secretes
larger amounts of interleukin (IL)-1, presents antigen, and mediates
MONOCYTOPENIA antibody-dependent cell-mediated cytotoxicity more efficiently. The
larger population, classical monocytes that are highly phagocytic and
proinflammatory, composes approximately 90 percent of blood mono-
cytes, and strongly expresses CD14 (lipopolysaccharide receptor) but
++
−
Marshall A. Lichtman does not express CD16 (FcγRIII), designated the CD14 CD16 subset.
lo
hi
These monocytes carry chemokine receptors CCR2 CX3CR1 . Of the
remaining monocyte population, approximately 5 percent exhibit strong
expression of CD14 and modest expression of CD16, the CD14 CD16
+
++
SUMMARY “intermediate” subset, which expresses the chemokine receptors
CCR2 CX3CR1 CCR5 , are proinflammatory and less phagocytic,
mid
mid
hi
The blood monocyte is in transit between the marrow and tissues where it and the “nonclassical” subset, which exhibits strong expression of CD16,
transforms (matures) into a macrophage. In tissues, the monocyte develops a the CD14 CD16 subset, which expresses the chemokines CCR CX-
lo
+
++
2
phenotype characteristic of the specific tissue of residence (e.g., Kupffer cells 3CR1 , the so-called patrolling subset. The latter subset contains den-
hi
3
of liver, microglia of brain, osteoclasts of bone). Because the monocyte partic- dritic cell precursors. The major subsets can each be further stratified
ipates in virtually all inflammatory and immune reactions, its concentration in based on the expression of CD64 (FcγRI) (Chaps. 67 and 68). 4
the blood may be increased in many such conditions, including autoimmune In tissues the monocyte is capable of transformation, under
diseases, gastrointestinal disorders, sarcoidosis, and several viral and bacterial the influence of local environmental factors, into a macrophage. The
infections. Monocytosis, an increase in the blood absolute monocyte count to monocyte plays an important role in acute and chronic inflammatory
reactions, including granulomatous inflammation; immunologic reac-
more than 800/μL (0.8 × 10 /L), may occur in some patients with cancer and tions, including those involved in delayed hypersensitivity; tissue repair
9
several unrelated conditions, such as postsplenectomy states, inflammatory and reorganization; atheroma and thrombus formation; and the reac-
bowel disease, and some chronic infections (e.g., bacterial endocarditis, tuber- tion to neoplasia and allografts. Because of the key role of monocytes
culosis, and brucellosis). The inconsistency and unpredictability in the blood in a variety of pathophysiologic reactions, a modest elevation in blood
monocyte concentration among patients with the same disease is a function monocyte count can occur in many disparate conditions. In addition, in
of its relatively small blood pool size, the damping effect of a large tissue circumstances in which large increases in the number of macrophages
pool, its relatively long life span, the number and complexity of effectors in are required in tissue sites, the demand may be met by local prolifera-
the relevant cytokine network that can influence the response, and the ability tion of macrophages and not be reflected either in an increased transit
to expand macrophage numbers by local mitosis in tissues. The most striking of monocytes through the blood compartment from marrow to tissue or
5
increase in blood monocyte concentration occurs with hematopoietic malig- in an increased concentration of blood monocytes. Occasionally, T-cell
nancies, especially clonal monocytosis, and monocytic or myelomonocytic clones release only macrophage/monocyte colony-stimulating factor
(M-CSF), which can stimulate the growth of macrophage colonies, pro-
leukemia. Depression, myocardial infarction, parturition, thermal injuries, and viding a model for local control of macrophage proliferation. 6
marathon competition are closely associated with monocytosis. Table 70–1
is a comprehensive list of causes of monocytosis. Monocytopenia is notable
in patients with aplastic anemia or hairy cell leukemia as a feature of pancy- NORMAL BLOOD MONOCYTE
topenia. Although other cytopenias accompany the monocytopenia, the latter CONCENTRATION
contributes significantly to the predisposition to infection and in hairy cell leu-
kemia is an aid to diagnosis because of its constancy. The MonoMAC syndrome, In the first 2 weeks of life, the average absolute blood monocyte count is
approximately 1000/μL (1 × 10 /L; Chap. 7). There is a gradual decline
9
the result of GATA2 mutations, is associated with extreme monocytopenia and in the normal monocyte count to a mean of 400/μL (0.4 × 10 /L) in
9
amonocytosis. adulthood, at which time monocytes constitute 1 to 9 percent (mean:
4 percent) of blood leukocytes (Chap. 2). Monocytosis is present when
the absolute count exceeds 800/μL (0.8 × 10 /L) in adults. Men tend
9
7
to have slightly higher monocyte counts than women. Increments in
The blood monocyte is a cell in transit from marrow to tissues. There the number of blood monocytes correlate directly with increases in the
1
are two major populations of blood monocytes based on physical prop- total blood monocyte pool and the monocyte turnover rate. The blood
8
erties: a smaller population thought to represent a less-mature stage, monocyte count cycles with a periodicity of 5 days. Older persons have
9
has a higher buoyant density, a smaller cell volume, lacks Fc receptors,
+
a decrease in the proportion of CD14 CD16 to CD14 CD16 mono-
+
−
++
cytes as compared to younger persons, although the functional signifi-
cance of this difference has not been established. 10
Acronyms and Abbreviations: CD, cluster of differentiation; G-CSF, gran-
ulocyte colony-stimulating factor; GM-CSF, granulocyte-monocyte col- DISORDERS ASSOCIATED WITH
ony-stimulating factor; IL, interleukin; LPS, lipopolysaccharide; M-CSF, MONOCYTOSIS
monocyte/macrophage colony-stimulating factor; MDS, myelodysplastic
syndrome; MonoMAC, monocytopenia and Mycobacterium avium complex; Table 70–1 outlines the diseases reported to be associated with mono-
NK, natural killer. cytosis. In one review, hematologic disorders represented more than
50 percent, collagen vascular diseases approximately 10 percent, and
malignant disease approximately 8 percent of cases of monocytosis. 11
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