Resistin-Like Molecule A and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure

Details

• Personal Author:
  Chen W-C ; Durmus N ; Grunig G ; Kwon S ; Marsh LM ; Nolan A ; Park S-H
• Description:
  Pulmonary hypertension (PH) has a high mortality and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type-2- and type-17 responses in C57BL/6 mice. Here, we focused on type-2-response-related cytokines, specifically resistin-like molecule (RELM)a, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild-type or RELMa-/- mice. Vascular remodeling was assessed with histology; right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were much more prominent in the C57BL/6 strain. Compared to wild-type mice, RELMa-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV IL-33-receptor were significantly increased in BALB/c wild-type mice, but not in BALB/c-RELMa-/- or in C57BL/6-wild-type or C57BL/6-RELMa-/- mice in response to antigen/PM2.5. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMa-/- mice were not different from their respective wild-type controls. The RELMa-/- animals demonstrated significantly decreased expression of RELMβ and RELMgamma, which makes these mice comparable to a situation where human RELMβ levels would be significantly modified, as only humans have this single RELM molecule. In BALB/c mice, RELMa was a key contributor to pulmonary vascular remodeling, increase in RV weight and RV cytokine responses induced by exposure to antigen/PM2.5, highlighting the significance of the genetic background for the biological role of RELMa. [Description provided by NIOSH]
• Subjects:
  Air Pollution Animals Antigens Immune System Occupational Health Particulate Matter Safety
• Keywords:
  Adaptive Immune Response Air Pollution Animal Studies Author Keywords: Resistin-like Molecule Cytokines Experimental Pulmonary Hypertension Immune Reaction Immune Response In Pulmonary Hypertension Molecular Biology Mouse Strains Particulates Pulmonary Hypertension Retnla Retnlb Retnlg Type 2 Inflammation Urban Fine Dust Urban PM

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• ISSN:
  1422-0067
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  24
• Issue:
  15
• NIOSHTIC Number:
  nn:20068531
• Citation:
  Int J Mol Sci 2023 Aug; 24(15):11918
• Contact Point Address:
  Gabriele Grunig, Division of Environmental Medicine, Department of Medicine, New York University Grossman School of Medicine (NYUGSoM), New York, NY 10016, USA
• Email:
  grunig01@nyu.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  International Journal of Molecular Sciences
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8db19d570ff9c7f61d2a9b26b42621b59aed7dddb6976bd00e8e9279b8a57d653a59d88f95e4934b7c3a2d789b3c3a36e9bfa270a0191ecb1c0e8e23f1c55f2c
• Download URL:
  https://stacks.cdc.gov/view/cdc/207143/cdc_207143_DS1.pdf
• File Type:
  [PDF - 4.40 MB ]