Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3956-3957
CORRESPONDENCE
Loss of Endothelial Surface Expression of E-Selectin
A Third
LAD Syndrome?
 |
LETTER |
To the Editor:
The recent report by DeLisser et al1 is very
interesting, proposing a third syndrome of human neutrophil
adhesion cascade defect. A child with severe recurrent
infections and low expression of E-selectin on blood vessel
endothelium caused by increase cleavage of E-selectin is
described. In contrast to the other 2 known syndromes, this
patient missed 2 of the main hallmarks of the syndromes: leukocytosis and persistent periodontitis.2,3 An
experimental model resembling this report is the E-selectin knockout
mice.4 In this model no leukocytosis is observed,
but in sharp contrast to the reported patient, the mice do not suffer
from severe infections. The clinical picture of the patient is
reminiscent of the severe form of leukocyte adhesion deficiency I (LAD
I). On the other hand, LAD II involving the selectin system has a
milder course.3
In the mouse model, it was shown that P-selectin can
compensate for the lack of E-selectin, and only when both selectins are blocked does a marked defect in neutrophil adhesion to the endothelium occur.4 With this in mind, how can the discrepancy between the clinical picture and the laboratory findings be explained? One
possible explanation not addressed in the report is persistent and
prolonged activation of neutrophils due to the continuous high blood
level of soluble E-selectin. This high level, which persisted when the
child was free of infection, could cause neutrophil activation.5 This activation may induce increased apoptosis of neutrophils leading to the observed neutropenia. To clarify this
situation, several additional studies could be performed. The
expression of activated epitopes of the CD18 molecule can be looked at
on unstimulated circulating neutrophils.6 Kinetic studies
investigating the half-life of the neutrophils may help to understand
the cause of the neutrophenia. Such studies were previously very informative in LAD I and LAD
II.7
Amos Etzioni
Division of Pediatrics
Rambam Medical Center
B. Rappaport School of Medicine
Technion, Haifa, Israel
| |
REFERENCES |
1.
DeLisser HM, Christofidou-Solomidou, Sun J, Nakada MT, Sullivan KE:
Loss of endothelial surface expression of E-selectin in a patient with recurrent infections.
Blood
94:884, 1999[Abstract/Free Full Text]
2.
Etzioni A, Harlan JM:
Leukocyte adhesion deficiency syndromes, in
Ochs HD,
Smith CIE,
Puck JM
(eds):
Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. Oxford, UK, Oxford University Press, 1999, p 375
3.
Etzioni A, Gershoni-Baruch R, Pollack S, Shehadeh N:
Leukocyte adhesion deficiency type II: Long-term follow-up.
J Allergy Clin Immunol
102:323, 1998[Medline]
[Order article via Infotrieve]
4.
Labow MA, Norton CR, Rumberger JM, Lombard-Gillooly KM, Shuster DJ, Hubbard J, Bertko R, Knaack PA, Terry RW, Harbison ML, Kontgen F, Stewart CL, McIntyre KW, Will PC, Burns DK, Wolitzky BA:
Characterization of E-selectin deficient mice: Demonstration overlapping function of the endothelial selectins.
Immunity
1:709, 1994[Medline]
[Order article via Infotrieve]
5.
Zimmerman GA, McIntry TM, Prescott SM:
Adhesion and signalling in vascular cell-cell interactions.
J Clin Invest
98:1699, 1996[Medline]
[Order article via Infotrieve]
6.
Araki M, Araki K, Miyazaki Y, Iwamoto M, Izui S, Yamamura K-I, Vassali P:
E-selectin binding promotes neutrohil activation in vivo in E-selectin transgenic mice.
Biochem Biophys Res Commun
224:825, 1996[Medline]
[Order article via Infotrieve]
7.
Price TH, Ochs HD, Gershoni-Baruch R, Harlan JM, Etzioni A:
In vivo neutrophil and lymphocyte function studies in a patient with leukocyte adhesion deficiency type II.
Blood
84:1635, 1994[Abstract/Free Full Text]
Response
The issue of peridontal disease is an important one. Our patient has
had chronic peridontitis, the severity of which has been mild, possibly
as a result of the long courses of antibiotics for her infections. We
do not disagree with Dr Etzioni that mechanisms other than the mere
absence of E-selectin from the endothelium may be responsible for this
patient's clinical syndrome, given mouse data which suggest that in
certain models of inflammation, P-selectin may be able to compensate
for the chronic absence of E-selectin. We, in fact, indicated this in
our discussion and suggested that the increased levels of soluble
(s)E-selectin may also be a factor in this patient that contributes
to leukocyte dysfunction. We are grateful to Dr Etzioni for indicating
another mechanism by which sE-selectin might be playing a role in this patient's clinical picture and his suggestions for further studies. With respect to studies of mice with targeted deletions of the selectins, we would note, as we indicated in our report, that there is
also evidence which suggests that P-selectin and E-selectin may have
some distinct, nonoverlapping functions,1,2 and as
others have done, would urge cau- tion in extrapolating data from murine knockout studies to humans.3,4
Horace M. DeLisser
University of Pennsylvania Medical
Center
Philadelphia, PA
Kathleen E. Sullivan
Children's Hospital of Philadelphia
Philadelphia,
PA
| |
REFERENCES |
1.
Munoz FM, Hawkins EP, Bullard DC, Beaudet AL, Kaplan SL:
Host defense against systemic infection with Streptococcus pneumoniae is impaired in E-, P-, and E-/P-selectin-deficient mice.
J Clin Invest
100:2099, 1997[Medline]
[Order article via Infotrieve]
2.
Kunkel EJ, Ley K:
Distinct phenotype of E-selectin-deficient mice. E-selectin is required for slow leukocyte rolling in vivo.
Circ Res
79:1196, 1996[Abstract/Free Full Text]
3.
Hynes RO:
Targeted mutations in cell adhesion genes: What have we learned from them?
Dev Biol
180:402, 1996[Medline]
[Order article via Infotrieve]
4.
Hynes RO, Wagner DD:
Genetic manipulation of vascular adhesion molecules in mice.
J Clin Invest
10:2193, 1996
