A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins

Estelle S. Harris, Ann O. Shigeoka, Wenhua Li, Roberta H. Adams, Stephen M. Prescott, Thomas M. McIntyre, Guy A. Zimmerman, Diane E. Lorant

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Leukocyte adhesion deficiency type I (LAD-1) is a disorder associated with severe and recurrent bacterial infections, impaired extravascular targeting and accumulation of myeloid leukocytes, altered wound healing, and significant morbidity that is caused by absent or greatly diminished surface expression of integrins of the β2 class. We report clinical features and analysis of functions of cells from a patient with a myelodysplastic syndrome and infectious complications similar to those in the severe form of LAD-1, but whose circulating neutrophils displayed normal levels of β2 integrins. Analysis of adhesion of these cells to immobilized ligands and to endothelial cells and assays of cell-cell aggregation and chemotaxis demonstrated a profound defect in adhesion mediated by β2 integrins indicative of a variant form of LAD-1. A novel cell line established from Epstein-Barr virus-transformed lymphoblasts from the subject demonstrated deficient β2 integrin-dependent adhesive function similar to that of the primary leukocytes. In addition, these cells had markedly impaired β1 integrin-dependent adhesion. Sequence analysis and electrophoretic mobility of β1 and β2 proteins from the cell line demonstrated that the defects were not a result of structural abnormalities in the integrin subunit chains themselves and suggest that the adhesive phenotype of these cells is due to one or more abnormalities of inside-out signaling mechanisms that regulate the activity of integrins of these classes. These features define a unique LAD-1 variant syndrome that may reveal important insights that are generally relevant to inside-out signaling of integrins, a molecular process that is as yet incompletely understood.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalBlood
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2001
Externally publishedYes

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Leukocyte-Adhesion Deficiency Syndrome
Integrins
Adhesion
Defects
Cells
Adhesives
Leukocytes
Cell Line
Immobilized Cells
Electrophoretic mobility
Cell Aggregation
Myelodysplastic Syndromes
Endothelial cells
Chemotaxis
Human Herpesvirus 4
Viruses
Bacterial Infections
Cell Adhesion
Wound Healing
Sequence Analysis

ASJC Scopus subject areas

  • Hematology

Cite this

Harris, E. S., Shigeoka, A. O., Li, W., Adams, R. H., Prescott, S. M., McIntyre, T. M., ... Lorant, D. E. (2001). A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins. Blood, 97(3), 767-776. https://doi.org/10.1182/blood.V97.3.767

A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins. / Harris, Estelle S.; Shigeoka, Ann O.; Li, Wenhua; Adams, Roberta H.; Prescott, Stephen M.; McIntyre, Thomas M.; Zimmerman, Guy A.; Lorant, Diane E.

In: Blood, Vol. 97, No. 3, 01.02.2001, p. 767-776.

Research output: Contribution to journalArticle

Harris, ES, Shigeoka, AO, Li, W, Adams, RH, Prescott, SM, McIntyre, TM, Zimmerman, GA & Lorant, DE 2001, 'A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins', Blood, vol. 97, no. 3, pp. 767-776. https://doi.org/10.1182/blood.V97.3.767
Harris, Estelle S. ; Shigeoka, Ann O. ; Li, Wenhua ; Adams, Roberta H. ; Prescott, Stephen M. ; McIntyre, Thomas M. ; Zimmerman, Guy A. ; Lorant, Diane E. / A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins. In: Blood. 2001 ; Vol. 97, No. 3. pp. 767-776.
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