Neutrophil accumulation at sites of
inflammation is mediated by specific groups of
cell adhesion molecules including the beta2 (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 beta2
integrins or
selectin carbohydrate ligands (eg,
sialyl-Lewis(x)). 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-Lewis(x). 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.