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

DOI PDF 被引用文献4件
  • Estelle S. Harris
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Ann O. Shigeoka
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Wenhua Li
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Roberta H. Adams
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Stephen M. Prescott
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Thomas M. McIntyre
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Guy A. Zimmerman
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.
  • Diane E. Lorant
    From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT.

抄録

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

収録刊行物

  • Blood

    Blood 97 (3), 767-776, 2001-02-01

    American Society of Hematology

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