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. 2023 Jun 8;24(7):1173–1187. doi: 10.1038/s41590-023-01522-0

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — Fibrin binding to CD11b-CD18 leads to the conversion of the integrin to the high-affinity extended-open (active) conformation that induces signal transduction in macrophages. This outside-in signaling is propagated by the formation of focal adhesions through recruitment and phosphorylation of scaffold proteins and signaling kinases such as paxillin and focal adhesion kinase (FAK) resulting in phosphorylation of PI3K and cytoskeleton organization. In parallel, the MAPK cascade MEK2 and ERK1/2 components are phosphorylated leading to 1) transactivation of NADPH oxidase complex (NOX2) and mitochondria responses to induce ROS release and oxidative stress, 2) phosphorylation of SMARCA5, NUP98, and the ERK1/2 nuclear transporter RANBP3 to regulate nuclear import, 3) phosphorylation of IRF2B2 regulating IFN signaling and 4) transcriptional activation of fibrin-induced genes involved in inflammatory, oxidative stress, and IFN-I responses. Phosphorylation (P); fibrin-induced proteins identified in this study, red filled shapes; fibrin-induced genes identified in this study are shown in box. Created with Biorender.com.