CHARACTERIZATION OF THE MOLECULAR BASIS FOR PMN DYSFUNCTION & RECURRENT INFECTION IN THE GP-138 DEFICIENCY SYNDROME

Abstract

A deficiency of a high MW glycoprotein present on the surface of normal PMNs, was found in unrelated patients (3 F, I M) with leukocytosis, periodontitis, & recurrent infection. Multiple adhesion-dependent functions including random and directed migration of affected PMNs were profoundly diminished. SDS-PAGE of NP-40 lysates of these PMNs and controls indicated that the deficient protein had a MW of 138,000 daltons. Further characterization showed the protein had a large carbohydrate content and was a major surface glycoprotein with a pI of 5.2-5.4. Galactose oxidase - NaB ³H₄ surface labeling demonstrated the three F were totally deficient in surface GP-138, but the M patient had 5-10% of normal on the PMN surface. Immunoprecipitation experiments with polyclonal anti-GP-138 on normal PMNs suggested that the functional protein consisted of two or more polypeptide chains. To further test this hypothesis, monoclonal antibodies against known leukocyte cell surface proteins were tested using fluorescent activated cell sorting (FACS). LFA-1, p150.95, and OKM1 as well as the beta subunit these polypeptides share, were absent in the two F tested. The M patient was identical except he had 30% of normal OKM1 by FACS. This data suggests GP-138 and OKM1 may be similar molecular species. Thus, PMN dysfunction in the GP-138 deficiency syndrome is related to impaired expression of at least three related high MW glycoproteins (OKM1, LFA-1, & p150.95) necessary for adhesion dependent cell function.

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