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 methionylleucyl-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.