Markus Wortmann1, Xianghui Xiao1, Guido Wabnitz2, Yvonne Samstag2, Maani Hakimi1,3, Dittmar Böckler1, Susanne Dihlmann4. 1. Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. 2. Institute for Immunology, Molecular Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. 3. Vascular Biobank Heidelberg (VBBH), Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. 4. Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. susanne.dihlmann@med.uni-heidelberg.de.
Abstract
OBJECTIVE AND DESIGN: Abdominal aortic aneurysm (AAA) is heavily infiltrated with leukocytes, expressing the DNA sensor absent in melanoma 2 (AIM2) and other inflammasome components. METHODS: Using multicolour flow cytometry, we here compared the expression of the inflammasome components AIM2, NLRP3, and ASC in different peripheral immune cells derived from AAA patients with those from non-AAA patients in a case-control study. In parallel, peripheral blood mononuclear cells (PBMC) of AAA patients and controls were stimulated in vitro with poly-dA:dT or lipopolysaccharide (LPS) to analyze inflammasome activation. RESULTS: AIM2 expression was significantly increased in peripheral granulocytes (P = 0.026), monocytes (P = 0.007), B lymphocytes (P < 0.0001), and T lymphocytes (P = 0.004) of AAA patients. Expression of other inflammasome components did not differ between the groups. Following in vitro stimulation with foreign DNA, PBMC derived from AAA patients released significantly more IL-1β (P = 0.022) into the supernatant than PBMC from control patients. In contrast, IL-1β release upon LPS stimulation did not differ between the PBMC groups. CONCLUSION: The data indicate the increased activation of an AIM2 inflammasome in peripheral immune cells of AAA patients and point to a systemic AIM2-associated immune response to AAA.
OBJECTIVE AND DESIGN:Abdominal aortic aneurysm (AAA) is heavily infiltrated with leukocytes, expressing the DNA sensor absent in melanoma 2 (AIM2) and other inflammasome components. METHODS: Using multicolour flow cytometry, we here compared the expression of the inflammasome components AIM2, NLRP3, and ASC in different peripheral immune cells derived from AAA patients with those from non-AAA patients in a case-control study. In parallel, peripheral blood mononuclear cells (PBMC) of AAA patients and controls were stimulated in vitro with poly-dA:dT or lipopolysaccharide (LPS) to analyze inflammasome activation. RESULTS:AIM2 expression was significantly increased in peripheral granulocytes (P = 0.026), monocytes (P = 0.007), B lymphocytes (P < 0.0001), and T lymphocytes (P = 0.004) of AAA patients. Expression of other inflammasome components did not differ between the groups. Following in vitro stimulation with foreign DNA, PBMC derived from AAA patients released significantly more IL-1β (P = 0.022) into the supernatant than PBMC from control patients. In contrast, IL-1β release upon LPS stimulation did not differ between the PBMC groups. CONCLUSION: The data indicate the increased activation of an AIM2 inflammasome in peripheral immune cells of AAA patients and point to a systemic AIM2-associated immune response to AAA.
Authors: Elizabeth Braunlin; Juan E Abrahante; Ron McElmurry; Michael Evans; Miles Smith; Davis Seelig; M Gerard O'Sullivan; Jakub Tolar; Chester B Whitley; R Scott McIvor Journal: Mol Genet Metab Date: 2022-02-03 Impact factor: 4.204