Aberrant activation and regulation of the oxidative burst in neutrophils with Mol glycoprotein deficiency.
Patients whose cells are deficient in the glycoproteins LFA-1, Mol, and p150,95 have recurrent infections and pronounced abnormalities in neutrophil adherence, aggregation, chemotaxis, and phagocytosis. We characterized activation and regulation of oxidative metabolism of Mol-deficient neutrophils. These cells failed to depolarize or to produce O2- or H2O2 normally when stimulated by opsonized zymosan. The chemotactic peptide formyl methionyl-leucyl-phenylalanine depolarized Mol-deficient neutrophils normally but caused supernormal production of O2- and H2O2, a result of a prolonged burst in oxidative metabolism. Phorbol myristate acetate depolarized Mol-deficient neutrophils at a nearly normal rate but evoked release of significantly less O2- and H2O2 than from normal PMN. The aberrant activation and regulation of the oxidative burst in Mol-deficient neutrophils are considered in light of recently emerging concepts in the cell biology of this process, and the possibility that these abnormalities reflect a defect in the cytoskeleton-membrane interaction is discussed.
D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D006023:Glycoproteins / Q000172:deficiency*; D006801:Humans; D007223:Infant; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption; D009195:Peroxidase / Q000378:metabolism; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism*; D017463:Receptors, Complement 3b; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D006023:Glycoproteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate