Increased degranulation of human myeloperoxidase-deficient polymorphonuclear leucocytes.
Myeloperoxidase (MPO)-deficient neutrophils (PMN) released considerably more beta-glucuronidase, lysozyme and vitamin B12-binding activities, when exposed to opsonized zymosan (STZ), than the normal counterpart. Release of the soluble enzyme lactate dehydrogenase was not appreciably changed over the incubation time with particles in either cell type. MPO-deficient PMN and normal PMN ingested STZ particles at a similar rate at early times, but thereafter phagocytosis by MPO-deficient PMN was significantly higher than that by normal PMN. The difference in degranulation between the two cell types greatly exceeded the difference in ingestion and was evident already at early phagocytosis times when no difference in phagocytosis was observed; this suggested that the higher degranulation in MPO-deficient PMN was at least in part independent of the increased ingestion. This was confirmed by experiments with the soluble stimulant N-formyl-L-norleucyl-L-leucyl-phenylalanine (FNLLP). MPO-deficient PMN and normal PMN exhibited a comparable respiratory burst when exposed to FNLLP plus cytochalasin B, but the defective cells released more azurophilic and specific granule markers than normal PMN. These results indicate that MPO-deficient PMN degranulate more than normal PMN and suggest a role for MPO in the regulation of degranulation.
Dri
P
P
Cramer
R
R
Menegazzi
R
R
Patriarca
P
P
D003594:Cytoplasmic Granules; D005966:Glucuronidase / Q000378:metabolism; D006098:Granulocytes / Q000201:enzymology; D006801:Humans; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D009195:Peroxidase / Q000172:deficiency*; D010544:Peroxidases / Q000172:deficiency*; D010587:Phagocytosis / Q000187:drug effects; D014805:Vitamin B 12 / Q000378:metabolism; D015054:Zymosan
D009842:Oligopeptides; C024998:N-formylnorleucyl-leucyl-4-phenylalanine; D015054:Zymosan; D010544:Peroxidases; D009195:Peroxidase; D009113:Muramidase; D005966:Glucuronidase; D014805:Vitamin B 12