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Myeloid-Related Protein-14/MRP-14/S100A9/Calgranulin B is Associated with Inflammation in Proliferative Diabetic
Ahmed M Abu El-Asrar1,2, Kaiser Alam1, Mohammad M Siddiquei1
1a Department of Ophthalmology , College of Medicine, King Saud University , Riyadh , Saudi Arabia.
Purpose:
To investigate the expression of the leukocyte proteins myeloid-related protein (MRP)-8 and MRP-14 in proliferative diabetic retinopathy (PDR) and the effect of MRP-8/MRP-14 (calprotectin) heterodimer on induction of proinflammatory factors in human retinal microvascular endothelial cells (HRMEC).
Methods:
Epiretinal membranes from 20 patients with PDR and 10 patients with proliferative vitreoretinopathy (PVR), vitreous fluid samples from PDR and non-diabetic subjects and HRMEC were studied by immunohistochemistry and Western blot analysis.
Results:
MRP-14 expression was localized in endothelial cells, leukocytes and myofibroblasts in all PDR membranes. MRP-8 expression was limited to intravascular leukocytes in 42% of the studied membranes. In PVR membranes, MRP-14 was expressed in leukocytes and myofibroblasts, whereas MRP-8 immunoreactivity was limited to leukocytes. MRP-14 was significantly upregulated in vitreous from PDR patients. MRP-8/MRP-14 (calprotectin) increased expression of intercellular adhesion molecule-1, but attenuated vascular cell adhesion molecule-1 expression in HRMEC.
Conclusions:
Increased MRP-14 levels are associated with inflammation in PDR.
Insights
Increased myeloid-related protein (MRP)-14 is linked to inflammation in proliferative diabetic retinopathy (PDR). This study investigated MRP-8 and MRP-14 expression and their impact on retinal cells, finding elevated MRP-14 in PDR patients.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness.
- Inflammation plays a critical role in the pathogenesis of DR, particularly proliferative diabetic retinopathy (PDR).
- Leukocyte proteins, such as myeloid-related proteins (MRP)-8 and MRP-14, are implicated in inflammatory processes.
Purpose of the Study:
- To examine the expression of MRP-8 and MRP-14 in PDR.
- To assess the impact of the MRP-8/MRP-14 (calprotectin) heterodimer on pro-inflammatory factor induction in human retinal microvascular endothelial cells (HRMEC).
Main Methods:
- Immunohistochemistry and Western blot analysis were performed on epiretinal membranes from PDR and proliferative vitreoretinopathy (PVR) patients.
- Vitreous fluid samples from PDR patients and non-diabetic controls were analyzed.
- HRMEC were treated with MRP-8/MRP-14 (calprotectin) to evaluate its effects.
Main Results:
- MRP-14 was expressed in endothelial cells, leukocytes, and myofibroblasts in PDR membranes, while MRP-8 was mainly in leukocytes.
- MRP-14 was significantly upregulated in the vitreous of PDR patients compared to controls.
- Calprotectin treatment of HRMEC increased intercellular adhesion molecule-1 (ICAM-1) expression but decreased vascular cell adhesion molecule-1 (VCAM-1) expression.
Conclusions:
- Elevated MRP-14 levels are associated with inflammation in PDR.
- MRP-8/MRP-14 (calprotectin) influences the expression of adhesion molecules in retinal endothelial cells, suggesting a role in PDR pathogenesis.
