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Neutrophil beta(2)-microglobulin and lactoferrin content in renal failure patients
1Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse, Wein, Austria. robert.deicher@nephro.imed3.akh-wien.ac.at
Abstract:
Multiple dysfunctions of polymorphonuclear leukocytes (PMNLs) contribute significantly to the increased morbidity and mortality among patients with end-stage renal disease. In the present study, we measured the PMNL content of beta(2)-microglobulin (beta(2)m) and lactoferrin in different states of renal insufficiency and after kidney transplantation. PMNLs were lysed ultrasonically and, after centrifugation, both proteins were assayed in the supernatant by enzyme-linked immunosorbent assay technique. Despite marked differences in plasma beta(2)m levels, no significant difference in PMNL content of beta(2)m and lactoferrin could be shown among the groups analyzed. There was also no correlation between plasma beta(2)m level and PMNL beta(2)m content. In control subjects, as well as in renal allograft recipients with a well-functioning graft, PMNL beta(2)m level correlated positively with PMNL lactoferrin level (pooled data, r = 0.55; P < 0.001; n = 55). Both proteins are considered to colocalize in peroxidase-negative PMNL granules. However, no correlation was found in the azotemic and uremic patient groups. Standard immunofluorescence staining of control PMNLs showed a cytoplasmic granular distribution of both granule proteins. However, in PMNLs of uremic patients, lactoferrin shifted to a perinuclear localization. PMNLs obtained from uremic individuals failed to elicit an increase in lactoferrin release after stimulation with the chemotactic peptide f-Met-Leu-Phe compared with PMNLs obtained from healthy volunteers. These data indicate abnormalities in uremic patients of PMNL granule lactoferrin content and release that are reversible after successful renal transplantation.
Insights
Polymorphonuclear leukocyte (PMNL) dysfunction in end-stage renal disease impacts patient outcomes. This study found altered lactoferrin localization and release in uremic patients, which improved after kidney transplantation.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- Polymorphonuclear leukocytes (PMNLs) exhibit dysfunctions in end-stage renal disease (ESRD), contributing to morbidity and mortality.
- Beta(2)-microglobulin (beta(2)m) is a marker associated with renal insufficiency, but its role within PMNLs in ESRD is unclear.
Purpose of the Study:
- To investigate the intracellular content and localization of beta(2)-microglobulin and lactoferrin in PMNLs from patients with varying degrees of renal insufficiency.
- To assess the impact of renal transplantation on PMNL protein content and function.
Main Methods:
- Quantitative analysis of beta(2)m and lactoferrin in lysed PMNLs using enzyme-linked immunosorbent assay (ELISA).
- Immunofluorescence staining to determine the subcellular localization of these proteins in PMNLs.
- Assessment of PMNL lactoferrin release in response to chemotactic peptide stimulation.
Main Results:
- No significant difference in PMNL beta(2)m or lactoferrin content was observed across different renal insufficiency stages.
- A positive correlation between PMNL beta(2)m and lactoferrin levels was found in healthy controls and transplant recipients, but not in uremic patients.
- In uremic patients, lactoferrin showed a perinuclear shift, and PMNLs exhibited impaired lactoferrin release upon stimulation, which normalized post-transplantation.
Conclusions:
- Uremia is associated with specific abnormalities in PMNL granule lactoferrin content and release.
- These PMNL functional deficits are reversible following successful kidney transplantation, suggesting a potential therapeutic target.