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Thermal regulation of FMLP receptors on human neutrophils
R B Coles1, R R Ranney, R J Freer
1Department of Pharmacology and Toxicology, School of Dentistry, Medical College of Virginia, Richmond 23298.
Abstract:
Polymorphonuclear leukocytes (PMNs) from subjects diagnosed as having juvenile periodontitis (JP) have been categorized on the basis of their chemotactic (CTX) response to f-met-leu-phe (FMLP) when assayed concurrently with PMNs from periodontally healthy subjects (HP). When PMNs from JP groups demonstrating depressed CTX were assayed for lysosomal enzyme secretion (LES) in response to FMLP, there were no significant differences with respect to rate or amount. Significant differences were observed between HP and chemotactically depressed JP cells when assessed for FMLP receptor ligand binding at 23 degrees C, but not at 4 degrees C. Receptor differences observed at 23 degrees C in HP cells included an increase in amount of total binding, number of receptors, and available displaceable binding sites, compared with the chemotactically depressed JP PMNs, whereas the receptor affinities were similar. These data suggest that differences in FMLP receptor density in JP PMN that are chemotactically depressed may be related to processes that modulate receptor mobility and/or expression.
Insights
Polymorphonuclear leukocytes (PMNs) from juvenile periodontitis (JP) patients show reduced chemotaxis (CTX) but normal lysosomal enzyme secretion (LES). FMLP receptor binding differences suggest altered receptor density in JP PMNs.
Area of Science:
- Immunology
- Oral Biology
- Cell Biology
Background:
- Juvenile periodontitis (JP) is characterized by severe periodontal destruction.
- Polymorphonuclear leukocytes (PMNs) play a crucial role in host defense against periodontal pathogens.
- Defective PMN function, including chemotaxis, has been implicated in JP pathogenesis.
Purpose of the Study:
- To investigate the functional characteristics of PMNs from JP patients.
- To compare chemotactic response, lysosomal enzyme secretion, and FMLP receptor binding in JP PMNs versus healthy controls.
- To elucidate the molecular mechanisms underlying PMN dysfunction in JP.
Main Methods:
- Isolation of PMNs from periodontally healthy (HP) and juvenile periodontitis (JP) subjects.
- Assay of PMN chemotaxis (CTX) in response to f-met-leu-phe (FMLP).
- Measurement of lysosomal enzyme secretion (LES) from PMNs stimulated with FMLP.
- Assessment of FMLP receptor ligand binding on PMNs at different temperatures (4°C and 23°C).
Main Results:
- PMNs from JP subjects exhibited significantly depressed chemotactic (CTX) responses to FMLP compared to HP.
- No significant differences in lysosomal enzyme secretion (LES) were observed between JP and HP PMNs.
- Significant differences in FMLP receptor ligand binding were found at 23°C, with HP PMNs showing increased total binding, receptor number, and available binding sites, but similar affinities.
- These receptor binding differences were not observed at 4°C.
Conclusions:
- The chemotactic defect in JP PMNs is not associated with impaired lysosomal enzyme secretion.
- Reduced FMLP receptor density, rather than affinity, may contribute to the chemotactic deficiency in JP PMNs.
- Altered FMLP receptor mobility and/or expression are suggested as underlying mechanisms for PMN dysfunction in juvenile periodontitis.
