Iodinating ability of various leukocytes and their bactericidal activity

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Phagocytic cells are crucial for innate immunity, engulfing and eliminating pathogens.
• The microbicidal activity of phagocytes involves complex biochemical processes, including the generation of reactive oxygen species and the action of enzymes like peroxidase.
• Understanding the kinetics of phagocytosis and the factors influencing microbicidal activity is essential for comprehending immune responses.

Purpose of the Study:

• To kinetically determine the ingestion of labeled particles, iodine fixation, and microbicidal activity in various phagocytic cells.
• To investigate the role of cellular peroxidase content in iodine fixation during phagocytosis.
• To compare the microbicidal activity and iodination capacity of phagocytes from normal individuals and those with chronic granulomatous disease.

Main Methods:

• Utilized monolayers of guinea pig and mouse phagocytic cells (polymorphonuclear leukocytes, mononuclear cells, macrophages).
• Employed radiolabeled particles ((14)C-labeled bacteria) and radioiodine ((131)I) to quantify ingestion and fixation.
• Assessed hydrogen peroxide generation potential via cyanide-insensitive NADH oxidase and measured peroxidase and catalase levels.

Main Results:

• Iodine fixation by phagocytes was strongly correlated with cellular peroxidase content, with mouse macrophages showing minimal fixation due to low peroxidase.
• Human polymorphonuclear leukocytes from patients with chronic granulomatous disease exhibited significantly reduced iodination compared to normal cells, correlating with lower microbicidal activity.
• While iodination capacity varied, mouse macrophages demonstrated effective bacterial killing, even without significant peroxidase activity or iodination.

Conclusions:

• Cellular peroxidase content is a key determinant of iodine fixation during phagocytosis.
• Impaired iodination, as seen in chronic granulomatous disease, is linked to reduced microbicidal activity.
• Phagocytic cells can exhibit potent microbicidal activity through mechanisms independent of significant peroxidase-mediated iodination, as exemplified by mouse macrophages.