Southampton Hospital,
Department of Pathology and Laboratory Medicine,
Southampton, NY
To the Editor:
We greatly enjoyed the elegant and informative study recently published
by Shi and colleagues.1 Using bromodeoxyuridine
(BrdU) labeling after severe endoluminal coronary artery
injury, the authors demonstrated activation and proliferation of
porcine adventitial fibroblasts that initially lacked actin expression.
Subsequently, the adventitial fibroblasts acquired actin expression
indicative of myofibroblastic differentiation, and these proliferating
adventitia-derived myofibroblasts were then shown to translocate the
gap between dissected media to contribute to neointima
formation. Smaller numbers of similar BrdU-positive nonmuscle cells
were demonstrated in the media as well. In their discussion, the
authors note that the precise mechanisms regulating fibroblast
migration to neointima are unknown.
It has been our experience2 3 4 and that of
others5 6 in human material that
endothelium and perivascular adventitial and
interstitial stromal dendritic fibroblast-like cells
express CD34, a transmembrane glycoprotein known as the
hematopoietic progenitor cell antigen.5 It is
increasingly thought that these cells are uncommitted stromal reserve
cells2 3 4 5 6 that, we feel, constitute the raw
material of the microvascular unit for use in repair, stromal
remodeling, and homeostasis. CD34 has a glycocalyceal mucin domain that
is a ligand for integrins, and thus CD34 may be involved in regulating
proadhesive and antiadhesive cellular
behavior.5 7 The intracytoplasmic domain of the
molecule is probably involved in signal transduction and cellular
differentiation5 and therefore might be involved
in regulation of phenotypic plasticity of CD34-positive adventitial
fibroblasts engaged in myofibroblastic differentiation. We have also
shown CD31 positive endothelial differentiation of
CD34-positive dendritic cells in cardiac
myxomas.4
In addition to being concentrated in the adventitia,
CD34-positive fibroblasts are also interspersed among the medial smooth
muscle cells in some vessels (personal observations). Thus, the
distribution of CD34-positive fibroblasts in human vessels is similar
to the distribution of BrdU-labeled adventitial and scattered medial
cells in the porcine material of Shi et al. In studies of
myofibroblastic differentiation of CD34-positive stromal cells in
mammary stromal tumors3 and in fibroma of tendon
sheath,2 we noted that increasing actin
expression in the tumor cells often correlated with CD34
downregulation. We wonder whether studying CD34 expression in the
porcine material of Shi et al might further elucidate the molecular
basis of adventitial myofibroblast differentiation and migration in
medial injury repair and neointima formation.
We are also interested in the role of dendritic stromal
histiocytes that express coagulation FXIIIa, the so-called
collagen-associated dendrophages of Nickoloff,8
in matrix remodeling and stromal repair as well as in
morphogenesis2 and
tumors.2 3 4 Transglutaminase FXIIIa is a potent
and pleiotropic fibroblast growth factor that regulates both fibroblast
proliferation and matrix protein synthesis and catalyzes polymerization
of matrix proteins including fibrin, fibronectin, and
collagens.9 10 FXIIIa coated on plastic causes
formation of actin-positive stress fibers in fibroblasts, modulates
novel cell spreading and adhesive behavior in fibroblasts and other
similarly grown normal and neoplastic cells, and induces
phosphorylation of tyrosine residues in 120- and 70-kD
proteins in these fibroblasts.11 Most normal
connective tissue contains scattered microvascular adventitial
FXIIIa-positive dendrophages,2 3 4 and these cells
are often markedly increased in inflammatory and reparative
processes.8 FXIIIa-positive dendrophages combine
with CD34-positive dendritic cells in a variety of mesenchymal
tumors,2 3 4 including the quasithrombotic
neoplasm cardiac myxoma.4 Thus, we suggest that
examination of the material of Shi et al from the standpoint of FXIIIa
reactivity to detect these important mitogenic
microvascular cells might also be informative with regard to the
mechanisms of myofibroblast differentiation and matrix remodeling in
neointima formation.
In conclusion, we applaud the excellent study of Shi and colleagues and
look forward to further molecular investigations into the processes of
microvascular myofibroblast differentiation and migration implicit in
their results.
References
1.
Shi Y, O'Brien JE, Fard A, Mannion JD, Wang D,
Zalewski A. Adventitial myofibroblasts contribute to
neointimal formation in injured porcine coronary
arteries. Circulation. 1996;94:1655–1664.
2.
Silverman JS, Knapik M. Fibroma of tendon sheath and
tendosynovial giant cell tumor are rich in factor XIIIa-positive
dendrophages. J Histotechnol. 1996;19:45–53.
3.
Silverman JS, Tamsen A. Mammary fibroadenoma and some
phyllodes tumor stroma are composed of CD34+ fibroblasts and factor
XIIIa+ dendrophages. Histopathology. 1996;29:411–419.[Medline]
[Order article via Infotrieve]
4.
Berrutti L, Silverman JS. Cardiac myxoma is rich in
FXIIIa+ dendrophages: immunohistochemical study of four cases.
Histopathology. 1996;28:529–536.[Medline]
[Order article via Infotrieve]
5.
van de Rijn M, Rouse RV. CD34: a review. Appl
Immunohistochem. 1994;2:71–80.
6.
Narvaez D, Kanitakis J, Faure M, Claudy A.
Immunohistochemical study of CD34-positive dendritic cells of human
dermis. Am J Dermatopathol. 1996;18:283–288.[Medline]
[Order article via Infotrieve]
7.
Delia D, Lampugnani MG, Resnati M, Dejana E, Aiello A,
Fontanella E, Soligo D, Prerotti MA, Greaves MF. CD34 expression is
regulated reciprocally with adhesion molecules in vascular
endothelium in vitro. Blood. 1993;81:1001–1008.
8.
Nickoloff BJ, Griffith CEM. The spindle-shaped cells
in cutaneous Kaposi's sarcoma histologic simulators include factor
XIIIa dermal dendrocytes. Am J Pathol. 1989;135:793–800.[Abstract]
9.
Toida M, Okumura Y, Swe Win KK, Oka N, Takami T, Adany
R. Characterization of cells containing factor XIII subunit a in benign
and malignant buccal lesions. Histochem J. 1995;27:449–456.[Medline]
[Order article via Infotrieve]
10.
Bruhn HD, Pohl J. Growth regulation of fibroblasts by
thrombin, factor XIII, and fibronectin. Klin Wochenschr. 1981;59:145–146.[Medline]
[Order article via Infotrieve]
11.
Ueki S, Takagi J, Saito Y. Dual function of
transglutaminase in novel cell adhesion. J Cell Sci. 1996;109:2727–2735.[Abstract]
© 1998 American Heart Association, Inc.
Correspondence
Whence Cometh Neointimal Myofibroblasts?
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