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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1616-1617
CORRESPONDENCE
To the Editor:
The mouse basophil, a rare and rarely recognized granulocyte
In a recent article,1 ultrastructural data were
used to identify defects in terminal differentiation of neutrophils in the CCAAT enhancer binding protein family of transcriptional factors knock-out mice (C/EBP / ). Peripheral blood of
C/EBP / and control mice was obtained from the
retro-ocular venous plexus and prepared for electron microscopy,
whereas the remainder of the molecular, functional, and biochemical
data in this report were obtained using bone marrow cells, peritoneal
cells elicited with thioglycollate injections, or the cell line U937
stably transfected with a zinc inducible C/EBP (p32)
expression vector, or empty vector. The electron micrographs
illustrated in figure 1A-B of Verbeek et al1 illustrate a
classic mature mouse basophil, not an immature neutrophil as stated, in
a C/EBP / mouse. The granules shown are typical for
histamine-containing mouse basophil granules,2-5 which are
less numerous and larger than mature granules in mature mouse
eosinophils and neutrophils2; basophils do not have
secondary and tertiary granules, as do neutrophils, and the
electron-lucent structures referred to as glutaraldehyde-extracted secondary granules are typical cytoplasmic vesicles and vacuoles, which
are present in basophils from multiple species (see this letter's
Figure).4-9 Figure 1C of
Verbeek et al1 shows a classic neutrophil from a control
mouse, as indicated in the legend. Whether or not the basophil
illustrated in Verbeeek et al's figure 1A-B represents a real increase
in this rare granulocyte class in C/EBP / mice
cannot be determined from the single cell presented here. Because much
of the molecular, functional, and biochemical data for defective
terminal neutrophil differentiation are based on studies of bone marrow
and elicited peritoneal exudate cells in C/EBP /
mice, it would be important to do ultrastructural studies of these cell
populations in these knock-out mice and their wild-type
controls.

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Electron micrograph shows a mature mouse basophil that was
present in the Fc R+ cells sorted from normal mouse bone
marrow.
(For more details, see Seder et al3
and Dvorak et al.4) The mature nucleus has heavily
condensed chromatin in 2 lobes. Small numbers of mature electron-dense
granules are evident in the cytoplasm. Numerous mitochondria and
electron-lucent secretory vesicles constitute the other
cytoplasmic organelles in this view. Original magnification,
× 23 000.
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The mouse basophil lineage was defined by ultrastructural analysis,
contrasted with developing mast cell, eosinophil, and neutrophil
lineages, and reported in 1982 in this journal.2 These
images clearly established the identification and evolution of these
lineages in this species and provided the necessary background for the
identification of mouse basophils as interleukin-4 (IL-4)-producing, high-affinity Fc R-positive, histamine-containing cells
sorted from mouse bone marrow and spleen,3 previously
referred to as non-B, non-T cells.10 The ultrastructural
characteristics of these basophils are described and contrasted with
those of Fc R-positive mast cells and with
Fc R-negative neutrophils and eosinophils in
detail.4 Further ultrastructural studies with this model
revealed that mouse basophils are Fc R-positive and
c-kit-negative, whereas mast cells are Fc R-positive and c-kit-positive, and that mouse basophils did not thrive in cultures supplemented with interleukin-3 (IL-3) or stem cell factor (SCF), on
the one hand, or with a combination of these 2 mouse mast cell growth
factors, on the other.5 In all of these
references,2-5 ultrastructural images of mouse basophils
identical to the basophil in Verbeek et al's figure 1A-B are included.
Ann M. Dvorak
Department of Pathology Beth Israel Medical Center
Boston, MA
References
1.
Verbeek W, Lekstrom-Himes J, Park DJ, et al.
Myeloid transcription factor C/EBP is involved in the positive regulation of lactoferrin gene expression in neutrophils.
Blood.
1999;94:3141-3150[Abstract/Free Full Text].
2.
Dvorak AM, Nabel G, Pyne K, Cantor H, Dvorak HF, Galli SJ.
Ultrastructural identification of the mouse basophil.
Blood.
1982;59:1279-1285[Free Full Text].
3.
Seder RA, Paul WE, Dvorak AM, et al.
Mouse splenic and bone marrow cell populations that express high-affinity Fc receptors and produce interleukin 4 are highly enriched in basophils.
Proc Natl Acad Sci U S A.
1991;88:2835-2839[Abstract/Free Full Text].
4.
Dvorak AM, Seder RA, Paul WE, Kissell-Rainville S, Plaut M, Galli SJ.
Ultrastructural characteristics of Fc R-positive basophils in the spleen and bone marrow of mice immunized with goat anti-mouse IgD antibody.
Lab Invest.
1993;68:708-715[Medline]
[Order article via Infotrieve].
5.
Dvorak AM, Seder RA, Paul WE, Morgan ES, Galli SJ.
Effects of interleukin-3 with or without the c-kit ligand, stem cell factor, on the survival and cytoplasmic granule formation of mouse basophils and mast cells in vitro.
Am J Pathol.
1994;144:160-170[Abstract].
6.
Dvorak AM.
Ultrastructural evidence for vesicular transport in basophil secretion.
Fundam Clin Immunol.
1995;3:17-28.
7.
Dvorak AM, MacGlashan DW Jr, Morgan ES, Lichtenstein LM.
Vesicular transport of histamine in stimulated human basophils.
Blood.
1996;88:4090-4101[Abstract/Free Full Text].
8.
Dvorak AM.
Cell biology of the basophil.
Int Rev Cytol.
1998;180:87-236[Medline]
[Order article via Infotrieve].
9.
Dvorak AM.
A role for vesicles in human basophil secretion.
Cell Tissue Res.
1998;293:1-22[Medline]
[Order article via Infotrieve].
10.
Ben-Sasson SZ, Le Gros G, Conrad DH, Finkelman FD, Paul WE.
Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines.
Proc Natl Acad Sci U S A.
1990;87:1421-1425[Abstract/Free Full Text].

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