FIGURE 2.

Leukocyte recruitment into the atherosclerotic plaque and infarcted tissue. (A) Initial endothelial dysfunction and activation is promoted by shear stress at sites of turbulent blood flow and lipid accumulation. While Ly6C^low monocytes patrol the endothelial surface for tissue surveillance, neutrophils and Ly6C^high monocytes are recruited into the subendothelial space. Within the plaque, Ly6C^high monocytes differentiate into macrophages. These proliferate, became foam cells, and orchestrate the inflammatory response, eventually die and build the necrotic core together with lipids and cholesterol crystals. These processes are further instructed by plaque-infiltrating T cells. Relevant inflammatory cytokines, chemokines, and receptor-ligand pairs for monocytes and T cells are indicated in the inlays. A third inlay shows CD40L binding to a distinct site within the I-domain of α_M chain of Mac-1 that does not interfere with other Mac-1 ligands. (B) Coronary artery occlusion precipitates MI and triggers progenitor and inflammatory leukocyte release from the bone marrow by adrenergic signaling and decreased expression of the retention factors CXCL12 and CXCR4 in the bone marrow niche. CXCL8 and CCL2 guide neutrophils and Ly6C^high monocytes to infarcted tissue. Neutrophils accumulate in the lesion by the adhesion factors depicted in the inlay and promote myocardial injury by reactive oxygen species (ROS), Hypochlorous acid (HClO), and NETs release. Ly6C^high monocytes are recruited and differentiate to macrophages. Tissue healing after MI is further modulated by infiltrated T cells that may secrete pro- or anti-inflammatory cytokines. LDL, low-density lipoprotein; oxLDL, oxidized LDL; Sel, Selectin; ESL1, E-Selectin Ligand 1; PSGL1, P-Selectin Glycoprotein Ligand 1; VCAM1, Vascular Cell Adhesion Molecule 1; VLA4, Very Late Antigen 4 (α₄β₁); ICAM1, Intercellular Adhesion Molecule 1; LFA1, Lymphocyte Function-associated Antigen 1 (CD11a/CD18, α_Lβ₂); Mac1, Macrophage Receptor 1 (CD11b/CD18, α_Mβ₂); PECAM1, Platelet/Endothelial Cell Adhesion Molecule 1; JAMs, Junctional Adhesion Molecules; CD40L, CD40 ligand; GPIbα, Platelet Glycoprotein Ibα; iC3b, inactive Complement component 3b; CCL, C-C Motif Chemokine Ligand; CXCL, C-X-C Motif Chemokine Ligand; CCR, C-C Motif Chemokine Receptor; CXCR, C-X-C Motif Chemokine Receptor; ROS, Reactive Oxygen Species; HClO, Hypochlorous acid; NETs, Neutrophil Extracellular Traps; IL, Interleukin; TNF, Tumor Necrosis Factor; INF, Interferon; G-CSF, Granulocyte Colony-Stimulating Factor; HSPCs, Hematopoietic Stem and Progenitor Cells. The figure was generated with schematics from BioRender.com.