Upregulation of respiratory burst of polymorphonuclear leukocytes by a bleomycin derivative, peplomycin.
The influence of peplomycin (PLM) on the respiratory burst of peripheral blood polymorphonuclear leukocytes (PMN) was investigated. Short-term (5 min) treatment of human PMN with 0.1mu g/ml to 100mu g/ml of PLM increased phorbol myristate acetate (PMA)- and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced luminol-dependent chemiluminescence. PMN, as well as alveolar macrophages from rabbits treated with 0.5 to 1.0 mg/kg of peplomycin per day for 5 days, generated more superoxide (O2-) than the cells from untreated rabbits. In both PLM-treated and untreated PMN, chemiluminescence induced by FMLP and PMA was decreased to less than 50% of the control by staurosporine, superoxide dismutase (SOD) and catalase. However, the peak intensity in PLM-untreated PMN was decreased to about 30% of the control by genistein, while this agent induced a slight decrease in peak intensity in the PLM-treated PMN. Inositol triphosphate and diacyl glycerol levels were not clearly increased by PLM, but an increase of intracellular Ca++ and a shift of protein kinase C (PKC) to the membrane occurred in PMN within 1 min after PLM treatment. Western blotting revealed that the tyrosine phosphorylation of a 115 kDa protein was upregulated by 5 to 50mu g/ml of PLM. While, PLM suppressed SOD activity in alveolar macrophages and PMN. These results seem to indicate that PLM increases the respiratory burst of PMN and macrophages both by way of direct PKC activation and by the upregulation of protein tyrosine phosphorylation. This increased reactive oxygen generation, together with the suppression of SOD activity seems to be tissue-impairing.
Ueta
E
E
Department of Oral Surgery, Kochi Medical School, Japan.
Osaki
T
T
Yoneda
K
K
Yamamoto
T
T
D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017663:Peplomycin / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D017663:Peplomycin