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Neutrophils isolated from leprosy patients release TNF-alpha and exhibit accelerated apoptosis in vitro
R B Oliveira1, M O Moraes, E B Oliveira
1Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brasil.
Abstract:
This study demonstrated that polymorphonuclear neutrophils (PMN) participate in the acute inflammatory response in leprosy as effector cells. Lepromatous patients present intense infiltrate of neutrophils in reactional (ENL) lesions. Circulating PMN of nonreactional patients, healthy donors, and reactional patients were purified and analyzed in vitro. The study confirmed the short lifespan of these cells in culture with progressive changes characteristic of apoptosis. Apoptosis was greatly accelerated in ENL patients as shown by cellular morphology, later confirmed by qualitative and quantitative analysis of fragmented DNA. It was observed that neutrophils stimulated with lipopolysaccharide, Mycobacterium leprae, and lipoarabinomannan secrete interleukin-8 and tumor necrosis factor alpha (TNF-alpha). Thalidomide, a drug known to inhibit TNF-alpha synthesis on monocytes, also exerted an inhibitory effect on TNF-alpha secretion in neutrophils. These data suggest that PMN can participate in the regulation of the immune response in leprosy and can contribute to the amplification of TNF-alpha production at the site of ENL lesion.
Insights
Polymorphonuclear neutrophils (PMN) are effector cells in leprosy inflammation. In erythema nodosum leprosum (ENL) lesions, PMN apoptosis accelerates, and they contribute to tumor necrosis factor alpha (TNF-alpha) amplification.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Polymorphonuclear neutrophils (PMN) are key inflammatory cells.
- Leprosy, particularly erythema nodosum leprosum (ENL) reactions, involves intense neutrophil infiltration.
- The role of PMN in leprosy pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of PMN as effector cells in the acute inflammatory response in leprosy.
- To analyze PMN apoptosis and cytokine secretion in leprosy patients, especially during ENL reactions.
- To assess the effect of thalidomide on PMN cytokine production.
Main Methods:
- Purification and in vitro analysis of circulating PMN from non-reactional leprosy patients, ENL patients, and healthy donors.
- Assessment of PMN lifespan and apoptosis using cellular morphology and DNA fragmentation analysis.
- Stimulation of PMN with lipopolysaccharide, Mycobacterium leprae, and lipoarabinomannan, followed by measurement of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) secretion.
Main Results:
- PMN exhibit a short lifespan in culture, with accelerated apoptosis observed in ENL patients.
- Stimulated PMN secrete interleukin-8 and TNF-alpha.
- Thalidomide inhibited TNF-alpha secretion by neutrophils, similar to its known effect on monocytes.
Conclusions:
- PMN function as effector cells in the acute inflammatory response of leprosy.
- Accelerated PMN apoptosis in ENL patients suggests a role in disease pathology.
- PMN contribute to TNF-alpha amplification at ENL lesion sites, and thalidomide may modulate this response.