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The 47-kD protein increased in neutrophil actin dysfunction with 47- and
89-kD protein abnormalities is lymphocyte-specific protein
T Howard, Y Li, M Torres, A Guerrero and T Coates
Department of Pediatrics, University of Alabama, School of Medicine,
Birmingham.
A male child born of related parents suffered recurrent infections because
of neutrophil actin dysfunction with increased amounts of a 47- kD protein
and decreased amounts of an 89-kD protein (NAD 47/89). The patient and
family members were studied to define the nature of the abnormal proteins
and to examine their role in the functional defects of neutrophil actin
dysfunction (NAD) 47/89 polymorphonuclear neutrophils (PMNs). NAD 47/89
PMNs are defective in motility, microfilamentous cytoskeletal structure,
and formyl peptide-induced actin polymerization and express increased
amounts of a 47-kD protein and decreased amounts of an 89-kD proteins
intermediate abnormality in amount of 47-kD and 89-kD proteins in PMNs from
parents and a female sibling suggest the disease is an autosomal recessive
disorder. Immunoblots with monoclonal antibody (MoAb1) and polyclonal
antibody raised to 47-kD protein showed the 89-kD protein is antigenically
distinct from the 47-kD protein and the 89-kD protein is not gelsolin.
125I-actin binding to one-dimensional (1 D) and 2 D gels of PMN proteins
from NAD 47/89 proband, family members, and controls showed the 47-kD
protein binds actin, is acidic (pl = 4.5 to 4.7), is recognized by the
MoAb1, exists on 2-D gels as three distinct actin binding species (MWapp 52
kD, 47-kD, and 44-kD), and is present in control PMNs in lesser amount than
in PMNs of NAD 47/89 proband or parents. Immunoaffinity purification of the
47 kD actin binding protein on MoAb1 matrix yielded a multimolecular
complex with proteins of MWapp 180 kD, 71 kD, 47 kD and actin. Cloning,
sequencing, and expression of a 1.58-kb cDNA selected for MoAb1 reactivity
from a HL60 expression library and microsequence of native PMNs, 47-kD
actin binding protein showed the overexpressed 47-kD protein is
lymphocyte-specific protein 1 (LSP1), which is a known actin binding
protein. The results show LSP1 is expressed in PMNs and suggest
overexpression of LSP1 is related to the motility and cytoskeletal
abnormalities in NAD 47/89 PMNs.
Volume 83,
Issue 1,
pp. 231-241,
01/01/1994
Copyright © 1994 by The American Society of Hematology
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