Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 884-894
Loss of Endothelial Surface Expression of E-Selectin in a
Patient With Recurrent Infections
Horace M. DeLisser,
Melpo Christofidou-Solomidou,
Jing Sun,
Marian
T. Nakada, and
Kathleen E. Sullivan
From the Pulmonary and Critical Care Division, University of
Pennsylvania Medical Center, Philadelphia, PA; Centocor, Malvern, PA;
and the Division of Immunologic and Infectious Diseases, Children's
Hospital of Philadelphia, Philadelphia, PA.
Neutrophil accumulation at sites of inflammation is mediated by
specific groups of cell adhesion molecules including the 
2 (CD18)
integrins on leukocytes and the selectins (P- and E-selectin on the endothelium and L-selectin on the leukocyte). This is supported by studies of patients with leukocyte adhesion deficiency syndromes whose leukocytes are genetically deficient in the expression of 2
integrins or selectin carbohydrate ligands (eg,
sialyl-Lewisx). However, inherited deficiency or
dysfunction of endothelial cell adhesion molecules involved in
leukocyte recruitment has not been previously described. In this report
we describe a child with recurrent infections and clinical evidence of
impaired pus formation reminiscent of a leukocyte adhesion deficiency
syndrome, but whose neutrophils were functionally normal and expressed
normal levels of CD18, L-selectin, and sialyl-Lewisx. In
contrast, immunohistochemical staining of inflamed tissue from the
patient showed the absence of E-selectin from the endothelium, although
E-selectin mRNA was present. However, E-selectin protein was expressed
as significantly elevated levels of circulating soluble E-selectin were
detected, the molecular size of which was consistent with a
proteolytically cleaved form of E-selectin. Gene sequencing failed to
show evidence of a secreted mutant variant. These data represent, to
our knowledge, the first description of a potentially inherited
dysfunction of an endothelial cell adhesion molecule involved in
leukocyte recruitment and provide additional human evidence of the
importance of endothelial selectins in the inflammatory response.
