Porphyrin-Induced Photodamage to Isolated Human Neutrophils

Abstract

Human neutrophils were irradiated with light at 34&380 nm in the presence of low concentrations of protoporphyrin or uroporphyrin. At increasing light doses or increasing concentrations of protoporphyrin. the neutrophils rapidly lost the ability of locomotion. Also, neutrophil chemiluminescence and hexose-monophosphate shunt activity rapidly declined. An early event was leakage of endogenous K + followed by lactate dehydrogenase and at a later stage leakage of particle-bound acid phosphatase. A number of cellular enzymes were inactivated, the susceptibility to inactivation decreased in the order: succinate dehydrogenase > lactate dehydrogenase > glutamate dehydrogenase > acid phosphatase. Uroporphyrin had no effect on neutrophil functions. leakage of K', or cellular enzymes. The results suggest that photodamage to the plasma membrane and the mitochondria are earlier events than photodamage to Iysosomes.

Selective Examination of Plasma Membrane–Associated Photosensitizers Using Total Internal Reflection Fluorescence Spectroscopy: Correlation between Photobleaching and Photodynamic Efficacy of Protoporphyrin IX

“…Due to preferential location of photosensitizer monomers in close vicinity to the plasma membrane, constituents of the plasma membrane have been suggested to be photodynamic targets (14). For PP, damage of the plasma membrane resulted in alterations of cell surface hydrophobicity (50) and amino acid transport (50) as well as leakage of K+ and lactate dehydrogenase (51).…”

Doxycycline Induced Photodamage to Human Neutrophils and Tryptophan

“…Neutrophil migration is dependent on extracellular glucose for ATP production (Weisdorf et al, 1982). This function is highly susceptible to external stimuli (HHkansson et al, 1980) and is easily damaged by protoporphyrin photosensitization of neutrophils (Sandberg et al, 1981). Glucose oxidation (by activation of the hexose monophosphate shunt) and chemiluminescence are sensitive parameters for phagocytic and bactericidal activity (Allen et al, 1972;Kjosen et al, 1976).…”

Alkaline Elution Studies of Hematoporphyrin‐derivative Photosensitized Dna Damage and Repair in Chinese Hamster Ovary Cells

“…Neither the suppression of [3H]dThd uptake nor any of the other subsidiary effects appears to be the sole primary cause for the loss of colony-forming ability, however. Mechanisms of cell killing (and synthesis inhibition) independent of either membrane damage or DNA damage can be envisioned, given the ability of p o r p h y r i n photosensitization t o damage polymerases (Munson and Fiel, 1977), mitochondria1 enzymes (Sandberg et al, 1981), and cytochrome P-450 (Dixit et al, 1983), for example. The remainder of this paper concerns porphyrin-photosensitized DNA damage without asserting that such damage is a major cause of cell death.…”