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Extracellular cytotoxicity by phagocytosing polymorphonuclear neutrophilic leukocytes: enhancement by a chemotactic
Abstract:
This study investigated the influence of a chemotactic stimulus on the extracellular cytotoxicity mediated by phagocytosing polymorphonuclear neutrophilic leukocytes (PMN). We used N-formyl-methionyl-leucyl-phenylalanine (FMLP) as chemotactic peptide, opsonized zymosan as phagocytosable particle, and ox red blood cells (ORBC) as extracellular bystander targets. Phagocytosing PMN were found to kill ORBC efficiently, as determined by the 51Cr-release assay. FMLP, at the concentration of 100 nM, significantly enhanced the target cell lysis. PMN from two patients with chronic granulomatous disease and normal PMN plus catalase or free radical scavengers (mannitol, benzoate, histidine) were completely devoid of cytolytic activity both in the presence and in the absence of FMLP. The results indicate that the target cell lysis by phagocytosing PMN as well as the chemotactic peptide-related amplification of the lysis itself depend on the expression of the PMN oxidative cytotoxic potential. A similar response to a chemotactic stimulus in vivo could provide a mechanism for regulating PMN-dependent cytotoxic and inflammatory processes.
Insights
Chemotactic stimuli amplify the killing power of polymorphonuclear neutrophils (PMN). This enhanced cytotoxicity relies on the oxidative potential of PMN, crucial for regulating inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Polymorphonuclear neutrophilic leukocytes (PMN) play a critical role in host defense.
- Extracellular cytotoxicity mediated by PMN is a key component of inflammatory processes.
- The influence of chemotactic stimuli on PMN-mediated cytotoxicity requires further elucidation.
Purpose of the Study:
- To investigate how chemotactic stimuli affect the extracellular cytotoxicity of phagocytosing PMN.
- To determine the role of oxidative potential in PMN-mediated lysis and its amplification by chemotactic peptides.
Main Methods:
- Utilized N-formyl-methionyl-leucyl-phenylalanine (FMLP) as a chemotactic peptide.
- Employed opsonized zymosan for phagocytosis and ox red blood cells (ORBC) as bystander targets.
- Quantified target cell lysis using the 51Cr-release assay.
- Assessed cytolytic activity in PMN from chronic granulomatous disease patients and with radical scavengers.
Main Results:
- Phagocytosing PMN demonstrated efficient lysis of ORBC.
- FMLP (100 nM) significantly enhanced the lysis of target cells.
- PMN lacking oxidative potential (CGD patients, catalase, or radical scavengers) showed no cytolytic activity, even with FMLP.
Conclusions:
- Extracellular cytotoxicity by phagocytosing PMN is dependent on their oxidative potential.
- Chemotactic peptide-induced amplification of PMN cytotoxicity requires the expression of oxidative cytotoxic potential.
- This mechanism may regulate in vivo PMN-dependent cytotoxic and inflammatory activities.