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Metal content of neutrophil granules is altered in chronic inflammation
R Hällgren1, N Feltelius, R Garcia
1Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Insights
Patients with inflammatory arthritis show increased granulocyte calcium, strontium, and iron. Manganese accumulates in granulocytes but not granules, while zinc decreases, highlighting metal storage differences in inflammatory conditions.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Chronic inflammatory conditions like arthritis are associated with cellular changes.
- Granulocytes play a key role in inflammatory responses.
- Elemental composition of granulocytes and their granules in inflammation is not fully understood.
Purpose of the Study:
- To quantify the mass fraction of key elements in granulocytes and their granule fractions from patients with active inflammatory arthritides.
- To compare elemental profiles between patients and healthy controls.
- To elucidate the role of specific granule subpopulations in metal storage during inflammation.
Main Methods:
- Isolation of granulocytes and their granule fractions (specific, light azurophil, dense azurophil) from patients (N=6) and controls (N=6).
- Measurement of mass fraction of calcium (Ca), strontium (Sr), manganese (Mn), iron (Fe), and zinc (Zn) using elemental analysis.
- Statistical comparison of elemental concentrations between patient and control groups.
Main Results:
- Significantly increased Ca in granulocytes and specific/light azurophil granules, but not dense azurophil granules, in patients.
- High concentrations of Sr in granulocytes and all granule fractions from patients, absent in controls.
- Increased granulocyte Mn in patients, with slight accumulation in specific granules but not azurophil granules.
- Prominent Fe accumulation in patient granulocytes and specific granules, absent in azurophil granules.
- Reduced granulocyte Zn and decreased Zn in dense/light azurophil granules, but normal in specific granules, in patients.
Conclusions:
- Granulocyte accumulation of Ca, Sr, and Fe during chronic inflammation correlates with their presence in specific granule subpopulations.
- Manganese accumulation in granulocytes during inflammation is not localized within their granules.
- Granule subpopulations exhibit distinct capacities for storing different metals, suggesting specialized roles in inflammatory processes.
Abstract:
The mass fraction of certain elements was measured in isolated granulocytes and isolated granulocyte granule fractions from patients with active inflammatory arthritides (N = 6) and healthy controls (N = 6). The patients had significantly increased amounts of Ca in the granulocytes, in the specific and light azurophil granules, but normal Ca amounts in the dense azurophil granules. Sr was below the detection limit in the granulocytes and granule fraction from controls, but it appeared in high concentrations in the granulocytes and all granule fractions from the patients. The patients had considerably increased granulocyte amounts of Mn but only slightly increased Mn concentrations in the specific granules. Mn was not detectable in azurophil granules from patients and controls. A prominent accumulation of Fe was seen in the granulocytes from the patients, together with an Fe accumulation in the specific granules. Fe was below the detection limit in azurophil granules from patients and controls. The patients had reduced granulocyte Zn and reduced amounts of Zn in the dense and light azurophil granules but normal Zn amounts in the specific granules. The results obtained indicate that the granulocyte accumulation of Ca, Sr, and Fe observed during chronic inflammation is associated with corresponding granule accumulation of these metals; the considerable Mn accumulation in granulocytes during inflammation is not localized in their granules; and the granule subpopulations differ in their capacity to store certain metals.