Porphyrin-Induced Photodamage to Isolated Human Neutrophils

Sandberg, Sverre; Glette, Johan; Hopen, G; Solberg, Claus Ola; Romslo, Inge

doi:10.1111/j.1751-1097.1981.tb09388.x

Cited by 41 publications

(3 citation statements)

References 42 publications

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“…This is also in accordance with our previous findings that doxycycline-induced photodamage to PMNLs, measured as impairment of their random migration, was mediated by the generation of singlet oxygen (24). We have previously shown, using protoporphyrin as a photosensitizer, that these species damage PMNLs (25,26). Doxycycline and demethylchlortetracycline seemed to be the most potent photosensitizers examined in our test system, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline were poor photosensitizers.…”

Section: Discussionsupporting

confidence: 79%

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes

Glette¹,

Sandberg²,

Haneberg³

et al. 1984

Antimicrob Agents Chemother

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When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 ,Ig/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.Polymorphonuclear leukocytes (PMNLs) are cornerstones of host defenses against infections. During phagocytosis and intracellular killing of bacteria by PMNLs, oxygen consumption takes place (16,20), and toxic oxygen radicals essential for the killing of phagocytosed bacteria (22, 27) are generated (1, 5). Several drugs, including tetracyclines, have been shown to influence these functions. However, studies with tetracyclines are inconsistent. High concentrations of chlortetracycline, doxycycline, and minocycline have been reported to markedly inhibit in vitro PMNL functions, whereas similar effects have not been demonstrated for oxytetracycline or tetracycline hydrochloride (15,18,19). We have previously shown that low concentrations (<10 pug/ml) of tetracyclines had no influence on in vitro PMNL functions, whereas high concentrations inhibited these functions. This inhibition was abolished when increasing concentrations of divalent cations were added to the medium (8, 9).Besides the chelating effect, tetracyclines may also influence PMNL function by other mechanisms. It is well known that these drugs can cause skin lesions in patients exposed to the sun (4,7,13,14,21,28), and we have recently shown that doxycycline can induce photodamage to PMNLs (24). In the present study, we examined the effect of six tetracyclines on PMNL oxygen consumption in the presence of UV light. In addition, the mechanism of tetracycline-induced photodamage was studied.MATERIALS AND METHODS Preparation of cells. Ten parts heparinized (18 U/ml) blood mixed with three parts dextran solution (60 mg/ml; Pharmacia, Uppsala, Sweden) were sedimented at room temperature. After centrifugation of the supernatant (500 x g, 5 min) the erythrocytes were lysed with ammonium chloride (0.15 M; pH 7.4), and the leukocytes (of which 60 to 80% were PMNLs) were washed twice in phosphate-buffered saline. The leukocytes were suspended in phosphate-buffered saline (pH 7.3) to a concentration of 107 cells per ml. Tetracycline was added to the ...

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Section: Discussionsupporting

confidence: 79%

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes

Glette¹,

Sandberg²,

Haneberg³

et al. 1984

Antimicrob Agents Chemother

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“…The effect of porphyrins as exogenous and endogenous sensitizers has been studied in a wide variety of biological environments and targets for the phototoxic damage, i.e., lipid and protein solutions (6,7), isolated erythrocyte membranes (8)(9)(10), whole erythrocytes (11-13), subcellular organelles (5,14,15), mammalian tissue and cell cultures (16)(17)(18) as well as animal (19,20) and human (21) models.…”

Section: Photodynamic and Non-photodynamic Actionmentioning

confidence: 99%

“…In turn, COPRO was more efficient in sensitizing mitochondrial damage than was URO, the most hydrophilic porphyrin (24). Further studies showed that the key determinants for the photodynamic effectiveness lie in the solubility properties of the porphyrin sensitizer relative to the hydrophilic or hydrophobic nature of the target biomolecules, with PROTO being most phototoxic to lipophilic structures, such as erythrocyte membranes, mitochondrial preparations and membrane- Oxygen bound enzymes, and URO more efficient in the photodamage to soluble structures (5,14,16).…”

Section: Photodynamic and Non-photodynamic Actionmentioning

confidence: 99%

The photodynamic and non-photodynamic actions of porphyrins

Afonso

Salamanca

Batlle

1999

Braz J Med Biol Res

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Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

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Effects of Porphyrins on Skin

Lim

2007

Ciba Foundation Symposium 146 ‐ Photosensitizing Compounds: Their Chemistry, Biology and Clinical Use

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Porphyrin-Induced Photodamage to Isolated Human Neutrophils

Cited by 41 publications

References 42 publications

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes

The photodynamic and non-photodynamic actions of porphyrins

Effects of Porphyrins on Skin

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