Impaired phagocytosis by alveolar macrophages from diabetic rats is related to the deficient coupling of LTs to the FcγR signaling cascade

Ferracini, Matheus; Martins, Joilson O.; Campos, M.R.M.; Anger, Denise B.C.; Jancar, Sônia

doi:10.1016/j.molimm.2010.04.018

Cited by 48 publications

(55 citation statements)

References 32 publications

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“…Previous studies of our group have suggested that using this animal model, AM showed impaired phagocytosis [11] and the treatment with insulin restored their function. Also, some inflammatory parameters such as cytokines expression (IL-6, CINC-1 and CINC-2) were restored by insulin [13].…”

Section: Discussionmentioning

confidence: 81%

“…Many mechanisms can relate predisposition to infection in diabetes and dysfunction of the innate immunity is considered one of the major explanations [23]. Important for antigen processing, AM are responsible for respiratory infections associated to DMI [11,24]. Most of the experimental literature has suggested that phagocytosis in macrophages and antigen presentation to T cells is impaired [11,25].…”

Section: Discussionmentioning

confidence: 99%

“…Important for antigen processing, AM are responsible for respiratory infections associated to DMI [11,24]. Most of the experimental literature has suggested that phagocytosis in macrophages and antigen presentation to T cells is impaired [11,25]. The autophagy pathway has been less studied in diabetic macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…When insulin was administrated, these cells did not restore previous levels of Atg 12. It is intriguing because insulin was capable of restoring AM phagocytosis [11]. Why insulin enhanced LC3 levels in AM but not in SM remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in alloxan-induced diabetic rats have also shown impairment in peripheral blood leukocyte phagocytic activities [9,10]. Using the same model, it was published that diabetic AM have impaired phagocytosis [11]. In patients, diabetic neutrophils have shown dysfunction on their chemotactic and phagocytic abilities [12] and some of these alterations are reversible after insulin treatment [13].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

Sunahara¹,

Nunes²,

Baptista

et al. 2014

Cell Physiol Biochem

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Background/Aims: Diabetes mellitus (DM) is characterized by hyperglycemia, associated to a lack or inefficiency of the insulin to regulate glucose metabolism. DM is also marked by alterations in a diversity of cellular processes that need to be further unraveled. In this study, we examined the autophagy pathway in diabetic rat macrophages before and after treatment with insulin. Methods: Bone marrow-derived macrophages (BMM), bronchoalveolar lavage (BAL) and splenic tissue of diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and control rats (physiological saline, i.v.). Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c.) 8 h before experiments. For characterization of the model and evaluation of the effect of insulin on the autophagic process, the following analyzes were performed: (a) concentrations of cytokines: interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-4, IL-10, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the BAL supernatant was measured by ELISA; (b) characterization of alveolar macrophage (AM) of the BAL as surface antigens (MHCII, pan-macrophage KiM2R, CD11b) and autophagic markers (protein microtubule-associated light chain (LC)3, autophagy protein (Atg)12 by flow cytometry and confocal microscopy (c) study of macrophages differentiated from the bone marrow by flow cytometry and confocal microscopy (d) histology of the spleen by immunohistochemistry associated with confocal microscopy. Results: Interestingly, insulin exerted antagonistic effects on macrophages from different tissues. Macrophages from bronchoalveolar lavage (BAL) enhanced their LC3 autophagosome bound content after treatment with insulin whereas splenic macrophages from red pulp in diabetic rats failed to enhance their Atg 12 levels compared to control animals. Insulin treatment in diabetic rats did not change LC3 content in bone marrow derived macrophages (BMM). M1 and M2 macrophages behaved accordingly to the host they were derived from. Diabetic M1 BMM had their LC3 vesicle-bound content diminished and M2 BMM enhanced their LC3 levels and insulin treatment failed to rescue autophagy to control levels. Insulin normalizes CINC-2 level but does not modulate autophagy markers. Conclusion: Taking these results together, diabetic macrophages derived from different compartments show different levels of autophagy markers compared to healthy animals, therefore, they suffer distinctively in the absence of insulin.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

Sunahara¹,

Nunes²,

Baptista

et al. 2014

Cell Physiol Biochem

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Diabetes and immunity to tuberculosis

2014

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Summary The dual burden of tuberculosis and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of tuberculosis. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to tuberculosis that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity which are potentially relevant to tuberculosis defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of tuberculosis in the diabetic population and relates them to recent advances in understanding the mechanistic basis of tuberculosis susceptibility and other complications of diabetes. Issues that merit further investigation, such as geographic host and pathogen differences in the diabetes/tuberculosis interaction, the role of hyperglycemia-induced epigenetic reprogramming in immune dysfunction and the impact of diabetes on lung injury and fibrosis caused by tuberculosis, are highlighted in this review.

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Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws

Nichols,

Pham,

Lee

et al. 2024

Cell. Mol. Life Sci.

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Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the distal limb during chronic diabetes. In 21-week-old Leprdb/db mice, increases were seen in mast cells/basophils, dermal γδ T cells, heterogeneous T cells, and Type 2 innate lymphoid cells. In addition, macrophages represented the largest cluster of immune cells and showed the greatest increase in genes associated with immune-specific pathways. Sub-clustering of macrophages revealed a bias toward angiogenic Lyve1+MHCIIlo macrophages in the hindpaws of 21-week-old diabetic mice, which corresponded to an increase in Lyve1+ macrophages in the hindpaws of 21-week-old diabetic mice on histology. Our results show that in Type 2 diabetes, the immunological function and phenotype of multiple immune cell types shift not only with metabolic disturbance, but also with duration of disease, which may explain the increased susceptibility to pathologies of the distal limb in patients with more chronic diabetes.

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Impaired phagocytosis by alveolar macrophages from diabetic rats is related to the deficient coupling of LTs to the FcγR signaling cascade

Cited by 48 publications

References 32 publications

Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

Diabetes and immunity to tuberculosis

Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws

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