BACKGROUND: Perivascular infiltrating mononuclear cells have been described in the vasculopathy found in multiple types of pulmonary arterial hypertension (PAH). We determined the expression of a specific type 1 immune response cytokine-chemokine cascade-interleukin (IL)-18 → (monokine induced by γ-interferon [MIG]/chemokine [C-X-C motif] ligand [CXCL] 9, interferon γ-induced protein [IP]-10/CXCL10 and interferon-inducible T-cell α chemoattractant [ITAC]/CXCL11)-in plasma samples from individuals with World Health Organization (WHO) Group 1 PAH. METHODS: We analyzed cytokine and chemokine protein levels in plasma from 43 individuals with WHO Group 1 PAH by enzyme-linked immunosorbent assay compared with 35 healthy individuals. Immunohistochemical studies on tissue specimens from WHO Group 1 PAH patients were performed for cytokines and chemokines and their respective receptors. RESULTS: Plasma IL-18 levels from WHO Group 1 PAH patients were significantly increased compared with healthy controls. Downstream chemokine CXCL10, but not CXCL9 or CXCL11, was markedly elevated compared with controls. Cellular sources of IL-18 were medial but not intimal smooth muscle cells. IL-18Rα was expressed from medial smooth muscle cells, endothelial cells, and mononuclear cells. CXCL10 and its main receptor, CXCR3, were expressed from infiltrating vascular wall mononuclear cells. CONCLUSIONS: These data suggest that augmented expression of IL-18 and CXCL10 may perpetuate an inflammatory milieu that eventually contributes to the vascular obstruction characteristic of PAH.
BACKGROUND: Perivascular infiltrating mononuclear cells have been described in the vasculopathy found in multiple types of pulmonary arterial hypertension (PAH). We determined the expression of a specific type 1 immune response cytokine-chemokine cascade-interleukin (IL)-18 → (monokine induced by γ-interferon [MIG]/chemokine [C-X-C motif] ligand [CXCL] 9, interferon γ-induced protein [IP]-10/CXCL10 and interferon-inducible T-cell α chemoattractant [ITAC]/CXCL11)-in plasma samples from individuals with World Health Organization (WHO) Group 1 PAH. METHODS: We analyzed cytokine and chemokine protein levels in plasma from 43 individuals with WHO Group 1 PAH by enzyme-linked immunosorbent assay compared with 35 healthy individuals. Immunohistochemical studies on tissue specimens from WHO Group 1 PAH patients were performed for cytokines and chemokines and their respective receptors. RESULTS: Plasma IL-18 levels from WHO Group 1 PAH patients were significantly increased compared with healthy controls. Downstream chemokine CXCL10, but not CXCL9 or CXCL11, was markedly elevated compared with controls. Cellular sources of IL-18 were medial but not intimal smooth muscle cells. IL-18Rα was expressed from medial smooth muscle cells, endothelial cells, and mononuclear cells. CXCL10 and its main receptor, CXCR3, were expressed from infiltrating vascular wall mononuclear cells. CONCLUSIONS: These data suggest that augmented expression of IL-18 and CXCL10 may perpetuate an inflammatory milieu that eventually contributes to the vascular obstruction characteristic of PAH.
Authors: David J Ross; Greg Hough; Susan Hama; Jamil Aboulhosn; John A Belperio; Rajan Saggar; Brian J Van Lenten; Abbas Ardehali; Mansoureh Eghbali; Srinivasa Reddy; Alan M Fogelman; Mohamad Navab Journal: Pulm Circ Date: 2015-12 Impact factor: 3.017
Authors: Andrew J Sweatt; Haley K Hedlin; Vidhya Balasubramanian; Andrew Hsi; Lisa K Blum; William H Robinson; Francois Haddad; Peter M Hickey; Robin Condliffe; Allan Lawrie; Mark R Nicolls; Marlene Rabinovitch; Purvesh Khatri; Roham T Zamanian Journal: Circ Res Date: 2019-03-15 Impact factor: 17.367
Authors: James D West; Eric D Austin; Elise M Rizzi; Ling Yan; Harikrishna Tanjore; Amber L Crabtree; Christy S Moore; Gladson Muthian; Erica J Carrier; David A Jacobson; Rizwan Hamid; Peggy L Kendall; Susan Majka; Anandharajan Rathinasabapathy Journal: Int J Mol Sci Date: 2021-05-09 Impact factor: 5.923