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Effects of lead on polymorphonuclear leukocyte (PMN) functions in occupationally exposed workers
M Valentino1, M Governa, I Marchiseppe
1Institute of Occupational Medicine, University of Ancona, Italy.
Abstract:
Previous in vitro experiments have shown that lead can inhibit PMN chemotaxis, phagocytosis and superoxide formation. Moreover, we have observed an inhibition of PMN chemotaxis in workers occupationally exposed to lead with a mean blood lead concentration of 3.06 mumol/l. The present study was carried out to evaluate locomotion and luminol assisted chemiluminescence (CL) of polymorphonuclear leukocytes (PMN) harvested from ten lead occupationally exposed workers with blood lead concentrations of 1.59 mumol/l (SD 0.27 mumol/l). Since lipids affect PMN activity and lipid composition is modified in erythrocytes of lead workers, PMN lipids were also studied. Ten healthy male subjects of the same age were taken as controls. Chemotaxis, i.e. locomotion stimulated through a specific membrane receptor, was impaired in the PMN of lead workers, but random migration, i.e. unstimulated cell locomotion, and respiratory burst were both unmodified. Cholesterol and phospholipids were not changed, but the percentage of arachidonic acid was significantly increased. The release of LTB4, generated by the oxidative metabolism of arachidonic acid, was increased. CL, which detects reactive oxygen species (ROS), was unmodified, but this lack of change could be the result of an increase in ROS, due to the augmentated percentage of arachidonic acid, and of a decrease in ROS, due to a direct inhibitory effect of lead on ROS generation. On the basis of the results from these ex vivo experiments, the conclusion that chemotaxis is the PMN function primarily affected by lead was confirmed. PMN are considered to be one of the first cellular targets for the action of lead; low exposure to lead modifies their activity and mainly modifies chemotaxis and LTB4 production.
Insights
Occupational lead exposure impairs polymorphonuclear leukocyte (PMN) chemotaxis, affecting cell movement towards specific signals. This study confirms lead primarily impacts PMN chemotaxis and leukotriene B4 production even at lower exposure levels.
Area of Science:
- Immunotoxicology
- Environmental Health
- Cellular Biology
Background:
- Lead exposure is known to affect immune cell function.
- Previous studies indicated lead inhibits polymorphonuclear leukocyte (PMN) functions like chemotaxis.
- Occupational lead exposure has been linked to altered PMN chemotaxis.
Purpose of the Study:
- To evaluate the effects of occupational lead exposure on PMN locomotion and luminol-assisted chemiluminescence (CL).
- To investigate alterations in PMN lipid composition, specifically arachidonic acid levels.
- To confirm if chemotaxis is the primary PMN function affected by lead exposure.
Main Methods:
- Harvesting PMNs from ten lead-occupationally exposed workers and ten healthy controls.
- Assessing PMN chemotaxis (stimulated locomotion) and random migration (unstimulated locomotion).
- Measuring respiratory burst activity and luminol-assisted chemiluminescence (CL) to detect reactive oxygen species (ROS).
- Analyzing PMN lipid composition, focusing on cholesterol, phospholipids, and arachidonic acid percentage.
Main Results:
- PMN chemotaxis was impaired in lead-exposed workers, while random migration and respiratory burst remained unmodified.
- While cholesterol and phospholipids were unchanged, the percentage of arachidonic acid in PMNs was significantly increased.
- Leukotriene B4 (LTB4) release was increased, suggesting enhanced oxidative metabolism of arachidonic acid.
- Luminol-assisted chemiluminescence (CL) was unmodified, potentially due to counteracting effects of increased arachidonic acid and lead's direct inhibition of ROS generation.
Conclusions:
- Occupational lead exposure primarily affects PMN chemotaxis, confirming previous findings.
- Low-level lead exposure modifies PMN activity, with significant impacts on chemotaxis and LTB4 production.
- PMNs are identified as early cellular targets for lead toxicity, with altered chemotaxis and lipid metabolism being key indicators.