Abstract. Mola (formerly gp 110) is a neutrophil glycoprotein whose deficiency is associated with abnormalities in several neutrophil functions, including defects in adherence, chemotaxis, and phagocytosis. Examination of whole cells and subcellular components by the use of both immunological and electrophoretic techniques demonstrated that Mo la was located primarily in the specific granules but that a small portion was present in the plasma membrane, where it is exposed to the extracellular environment and can bind to anti-Mo 1 antibody. During degranulation, Mola is translocated from the specific granules to the plasma membrane, resulting in a 5-10-fold increase in the surface expression of this glycoprotein. These findings plus previous work suggest that plasma membrane-associated Mole is needed for a normal interaction between neutrophils and underlying surfaces, and raise the possibility that the increase in surface adhesiveness of neutrophils that have discharged their specific granules might be due in part to the increase in the amount of Mo 1a in the plasma membranes of these degranulated cells.
Neutrophils from a five-year-old boy with recurrent bacterial infections failed to spread on surfaces, leading to a severe defect in chemotaxis and a mild impairment in phagocytosis. Failure to spread was also seen in a fraction of the neutrophils from the patient's mother and sister, but cells from his father and brother were normal. Gel electrophoresis revealed that a protein with a molecular weight of 110,000 daltons (designated gp 110) present in the particulate fraction of normal neutrophils was absent from the patient's cells, and that its levels were below normal in cells from his mother and sister but normal in neutrophils from his father and brother. These findings suggest that gp 110 is necessary for the spreading of neutrophils onto surfaces, that the functional abnormality in the patient's cells is caused by its absence, and that deficiency of gp 110 is an X-linked congenital disease.
A B S T R A C T Evidence was obtained regarding the way the 02-forming NADPH oxidase of human neutrophils is arranged within the plasma membrane. 02 production by particles from zymosan-activated human neutrophils rose two-to threefold when the particles were assayed in the presence ofappropriate concentrations of Triton X-100. The portion of activity revealed by the detergent was not affected by treating the particles with trypsin or with p-chloromercuribenzene sulfonate, a nonpenetrating sulfhydryl reagent, but the activity detectable in the absence of detergent was abolished by these treatments. 0°production by phagocytic vesicles was not augmented by detergent, and was almost entirely eliminated by tryptic digestion of the vesicles regardless of whether or not detergent was present during the assay. These results suggest that the 02-forming oxidase is embedded in the plasma membrane with a portion extending into the cytoplasm and the rest buried in the lipid bilayer. It is proposed that the pyridine nucleotide-binding site is located on the cytoplasmic extension and the oxygen binding site is on the intramembranous portion of the enzyme. INTRODUCTION When a microorganism is ingested by a neutrophil, it becomes tightly enclosed within a vesicle whose wall consists of a portion of what was originally the plasma membrane of the phagocyte. Within this plasma membrane is an oxidase that catalyzes the one-electron reduction of oxygen to°2 at the expense of NADPH
A B S T R A C T These studieswere produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis.The fraction of T4 degraded by ELC was decreased by the addition of unlabeled T4 and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H202) is a necessary cofactor in the reaction. From these findings we conclude the following: (a) ELC is the major pathway for the degradation of T4 during leukocyte phagocytosis, and accounts for 50% of the disposal of this iodothyronine; (b) the NEI and iodide formed by phagocytosing cells are derived from the degradation of the phenolic and tyrosyl rings of T4, although ELC per se accounts for only a small fraction of these iodinated products; (c) the process by which ELC occurs is enzymic in nature, and its occurrence requires the presence of the respiratory burst that accompanies phagocytosis; (d) the enzyme responsible for ELC is likely to be a peroxidase, although a clear role for myeloperoxidase as the candidate en-J. Clin. Invest.
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