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.

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