Expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron during cellular immune activation

Koorts, Alida Maria; Levay, PF; Hall, A. N.; Merwe, C.F. van der; Becker, P. J.; Viljoen, Margaretha

doi:10.1016/j.bcmd.2011.04.006

Cited by 6 publications

(8 citation statements)

References 39 publications

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“…40,41 Furthermore, cytokines differentially regulate the expression of the ferritin subunits, and it is mostly the H-subunit of ferritin that is increased by cytokine induction at variance with the L-subunit. [40][41][42][43][44] As the expression of the ferritin subunits are also influenced by proinflammatory cytokines, 21 the proinflammatory status of the patients was investigated by measuring CRP, and proinflammatory and anti-inflammatory cytokines in the plasma. CRP concentrations were not significantly different between the osteoarthritis and the control group and both were within normal limits for plasma CRP.…”

Section: Discussionmentioning

confidence: 99%

“…Although it has on occasion been used as a therapeutic tool, application of TGF-β causes other problems in tissues of the joints and is said to contribute to fibrosis and osteophyte formation. 46 It is generally accepted that proinflammatory cytokines contribute to the up-regulation of the expression of the H-subunit of ferritin, 21 but very little is known about an association between ferritin subunits and TGF-β. In the present study, the anti-inflammatory cytokine, TGF-β, was significantly increased without any overt indication of proinflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

“…Fixation of bone marrow tissue and immunolabelling of the H- and L-subunits of ferritin were performed as described elsewhere. 20,21…”

Section: Methodsmentioning

confidence: 99%

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Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

Koorts

Levay

Hall

et al. 2012

Exp Biol Med (Maywood)

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Osteoarthritis is a disease characterized by an increase in the production of reactive oxygen species (ROS) in afflicted joints. Excess iron, due to its role in the production of ROS and crystal deposition in the joints, is implicated in the disease progression of osteoarthritis. Ferritin is a major regulator of the bioavailability of iron, and its functions are determined largely by the combination of H- and L-subunits present in its outer protein shell. The purpose of the study was to investigate the expression of the H- and L-subunits of ferritin in bone marrow macrophages of osteoarthritis patients. The cytokine profiles were assessed as cytokines play an important role in the expression of the ferritin subunits. The H-subunit of ferritin in the bone marrow macrophages was significantly higher ( P value = 0.035) in the osteoarthritis patients compared with the controls (107.84; 69.25–167.94 counts/ μm2; n= 7 versus 71.07; 58.56–86.26 counts/ μm2; n= 19). A marginally significant increase ( P value = 0.059) was shown for the expression of the L-subunit in the osteoarthritis patients compared with the controls (133.03; 104.04–170.10 counts/ μm2; n= 7 versus 104.23; 91.53–118.70 counts/ μm2; n= 19). The osteoarthritis and control groups had comparable C-reactive protein, as well as proinflammatory and anti-inflammatory cytokine concentrations. The major exception was for transforming growth factor- β (TGF- β), which was higher ( P value = 0.014) in the plasma of the osteoarthritis patients (16.69; 13.09–21.28 ng/mL; n= 7 versus 8.60; 6.34–11.67 ng/mL; n= 19). Up-regulation of the ferritin subunits decreases the levels of bioavailable iron and provides protection against the unwarranted production of ROS and crystal deposition. A role for TGF- β in the up-regulation of the expression of the H-subunit, and possibly the L-subunit, of ferritin is postulated in osteoarthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

Koorts

Levay

Hall

et al. 2012

Exp Biol Med (Maywood)

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“…Neopterin levels are generally considered as an indication of both macrophage function and cell mediated immunity. It is said that when cell-mediated immunity dominates, circulating neopterin levels are usually high and when humoral immunity dominates, neopterin levels are low [3][4][5][6][7][8][9][10][11] . Abundant evidence exists for neopterin levels to be increased in disturbances marked by inflammatory activity and raised neopterin levels and increases with disease progression, have previously been described 12 .…”

Section: Neopterin As Indicator Of Inflammatory (Cellular Immunity) Smentioning

confidence: 99%

“…In the present study the value of neopterin as general marker of the inflammatory status was examined by comparing neopterin levels to that of two other recognised biomarkers of inflammation, i.e., CRP and IL-6 6, [11][12][13] . As seen in Table 2, the mean neopterin levels were significantly higher than that of the control group for both the HAART-naïve (p<0.001) and the HAART (p<0.001) groups.…”

Section: Neopterin As Indicator Of Inflammatory (Cellular Immunity) Smentioning

confidence: 99%

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

Bipath¹,

Levay²,

Olorunju³

et al. 2015

Afr H. Sci.

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Abstract:Background: A general non-specific marker of disease activity that could alert the clinician and prompt further investigation would be of value in patients with HIV/AIDS, especially in resource limited environments. Objective: To investigate the potential of neopterin as non-specific biomarker in patients with advanced HIV/AIDS. Methods: Cross-sectional study in 105 HIV positive patients (75 on highly active antiretroviral treatment (HAART). Neopterin was assessed by enzyme linked immune-absorbent assay and cytokines by flow cytometry. Results: Neopterin levels were significantly higher (p<0.001) for the total patient than for the control group. Significant correlations between neopterin and plasma indicators of inflammation showed neopterin to be a good indicator of active inflammatory status and of the effect of HAART on the immune system. Neopterin was superior to C-reactive protein and to individual cytokines as indicator of immune deficiency. Increased neopterin levels were associated with a decline in albumin, haemoglobin and the albumin/globulin ratio, and with increases in red cell distribution width. Conclusions: Plasma neopterin is a good non-specific biomarker of disease activity in HIV/AIDS patients. It is a good indicator of inflammatory activity, perpetuation of inflammation-associated co-morbidities, degree of immune deficiency and has predictive value for underlying disease, and for monitoring the HAART response.

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Unveiling the stochastic nature of human heteropolymer ferritin self‐assembly mechanism

Bou‐Abdallah,

Fish,

Terashi

et al. 2024

Protein Science

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Despite ferritin's critical role in regulating cellular and systemic iron levels, our understanding of the structure and assembly mechanism of isoferritins, discovered over eight decades ago, remains limited. Unveiling how the composition and molecular architecture of hetero‐oligomeric ferritins confer distinct functionality to isoferritins is essential to understanding how the structural intricacies of H and L subunits influence their interactions with cellular machinery. In this study, ferritin heteropolymers with specific H to L subunit ratios were synthesized using a uniquely engineered plasmid design, followed by high‐resolution cryo‐electron microscopy analysis and deep learning‐based amino acid modeling. Our structural examination revealed unique architectural features during the self‐assembly mechanism of heteropolymer ferritins and demonstrated a significant preference for H‐L heterodimer formation over H‐H or L‐L homodimers. Unexpectedly, while dimers seem essential building blocks in the protein self‐assembly process, the overall mechanism of ferritin self‐assembly is observed to proceed randomly through diverse pathways. The physiological significance of these findings is discussed including how ferritin microheterogeneity could represent a tissue‐specific adaptation process that imparts distinctive tissue‐specific functions to isoferritins.

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Expression of the H-subunit and L-subunit of ferritin in bone marrow macrophages and cells of the erythron during cellular immune activation

Cited by 6 publications

References 39 publications

Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

Expression of the H- and L-subunits of ferritin in bone marrow macrophages of patients with osteoarthritis

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

Unveiling the stochastic nature of human heteropolymer ferritin self‐assembly mechanism

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