Blood, Vol. 92 No. 8 (October 15), 1998:
p. 2971
CORRESPONDENCE
Catecholaminergic Regulation of Hematopoiesis in Mice
 |
LETTER |
To the Editor:
The article by Benestad et al1 published in
BLOOD states that murine bone marrow functions are not
regulated by neuronal mechanisms. I am surprised by this drastic and
final conclusion. Even the title, "No Neuronal Regulation of Murine
Bone Marrow Function," sounds more suitable for a popular press
article.
Actually, there are a number of observations that have been disregarded
by the investigators and some most recent findings that should be taken
in consideration.
(1) A recent publication that has been ignored by the investigators
shows that surgical denervation decreases femoral cellularity as well
as progenitor cells while mobilizing these cells in the peripheral
blood of splenectomized mice. In nonsplenectomized animals, these
changes were quickly cleared.2 In addition, Benestad et
al1 did find a decreased bone marrow cellularity in
chemical sympathectomized mice.
(2) The investigators argue that our results with adrenergic agonists
and antagonists that suggest the presence of a catecholaminergic regulation of haemopoiesis are due to nonspecific effects. This seems
rather superficial, because, besides the findings quoted, we
demonstrated also that (a) bone marrow pre-B cells do express 
1B-adrenergic receptors,3-5 (b) that in
vitro norepinephrine (NE) and other adrenergic agonists can inhibit
myelopoiesis and rescue bone marrow progenitors from the toxic effect
of cytotoxic drugs, and that the 1-adrenergic antagonist prazosin
neutralizes these effects at concentrations of 10
10 to
1012 mol/L.3,6 (c) NE protects 77% of mice
injected with a supralethal dose of carboplatin (200 mg/kg) and
prazosin abolishes the protection. A time-course study showed that this
effect was exerted directly on hematopoietic progenitors in the bone
marrow.6
Most recently, we demonstrated that murine bone marrow contains
substantial amounts of catecholamines. NE and dopamine (DA) showed a
daily rhythmicity, with peak values during the night. The rhythm was
disrupted by chemical sympathectomy, whereas epinephrine (E) did not
show any rhythmicity or sensitivity to 6-hydroxydopamine. High and low
values of NE and DA were associated with high and low values of their
metabolites, which indicated a rhythmic catecholamine release. NE but
not DA and E was positively associated with the proportion of cells in
the G2/M and S phases of the cell cycle. Moreover, NE and DA were found
in both short-term and long-term bone marrow cultures as well as in
human or murine B-lymphoid cell lines. These findings indicate that
endogenous catecholamines in the bone marrow have both neural and
cellular origin.5
In conclusion, the negative results obtained by Benestad et
al1 might well reflect a long-term adaptative response of
bone marrow cells catecholamines, but in no case can rule out a
neuronal influence on hematopoiesis. Finally, as the investigators also beautifully show, bone marrow is richly innervated by afferent adrenergic fibers. Should we argue that such rich innervation is
useless?
Georges J.M. Maestroni
Istituto Cantonale di
Patologia
Center for Experimental Pathology
Locarno,
Switzerland
| |
REFERENCES |
1.
Benestad HB,
Strøm-Gundersen I,
Iversen PO,
Haug E,
Njå A:
No neuronal regulation of murine bone marrow function.
Blood
91:1280,
1998[Abstract/Free Full Text]
2.
Afan AM,
Broome CS,
Nicholls SE,
Whetton AD,
Miyan JA:
Bone marrow innervation regulates cellular retention in the murine haemopoietic system.
Br J Haematol
98:569,
1997[Medline]
[Order article via Infotrieve]
3.
Maestroni GJM,
Conti A:
Modulation of hematopoiesis via alpha-1 adrenergic receptors on bone marrow cells.
Exp Hematol
22:314,
1994
4.
Maestroni GJM,
Conti A:
Noradrenergic modulation of lymhohematopoiesis.
Int J Immunopharmacol
16:117,
1994[Medline]
[Order article via Infotrieve]
5. Maestroni GJM, Cosentino M, Marino F, Togni M, Conti A, Lecchini
S, Frigo G: Neural and endogenous catecholamines in the bone marrow.
Circadian association of norepinephrine with percentage of cells in
G2/M. Exp Hematol (in press)
6.
Maestroni GJM,
Togni M,
Covacci V:
Norepinephrine protects mice from acute lethal doses of carboplatin.
Exp Hematol
25:491,
1997[Medline]
[Order article via Infotrieve]
