Figure 8.

Depletion of cardiac macrophages (Mϕ) leads to decreased cardiac function. A, cytometry by time-of-flight (CyTOF)–based quantification of cardiac immune cells (left), visualized stochastic neighbor embedding (ViSNE) plot showing the abundance of different immune cells and colored expression of CD64 in arbitrary units (AU, middle), and quantification of immune cell abundance (right) 6 wk after transverse aortic constriction (TAC) surgery in isotype or α-CD115 antibody administration (n=4). Statistical significance between the isotype and α-CD115 antibody–treated groups by cell type was determined by 2-tailed Mann-Whitney U tests. B, Representative CyTOF plots (left) showing cardiac resident Mϕs (Res Mϕs) and monocyte-derived Mϕs (MoMFs) gated based on CD11b (integrin alpha M) and CD64. The dot color represents the level of CCR2 (C-C chemokine receptor type 2), TIMD4 (T-cell immunoglobulin and mucin domain containing 4), and CX3CR1 (C-X3-C motif chemokine receptor 1) expression. Quantification (right) of Res Mϕs and MoMFs 6 wk after TAC in mice which received isotype or α-CD115 antibody administration (n=4). Statistical significance between the isotype and α-CD115 antibody–treated groups was determined by 2-tailed Mann-Whitney U tests. C, Cardiac hypertrophy (left, heart weight [HW] to body weight [BW] ratio), ejection fraction (middle), and fractional shortening (right) in sham and TAC mice after isotype or α-CD115 antibody administration (n=5, 4, 6, 6). Statistical significance was evaluated by a 2-way ANOVA. All pairwise comparisons were made. Tukey tests were used to correct for multiple comparisons. D, Representative images (left) and area quantification (right) of WGA (wheat germ agglutinin)-stained sections from isotype or α-CD115 antibody administered mice 6 wk after sham and TAC (n=5, 4, 6, 6). Statistical significance was evaluated by a 2-way ANOVA. All pairwise comparisons were made. Tukey tests were used to correct for multiple comparisons. E, Representative images (left) and quantification (right) of Masson Trichrome-stained (MTC) sections from isotype or α-CD115 antibody administered mice 6 wk after sham and TAC (n=5, 4, 6, 6). Statistical significance was evaluated by a 2-way ANOVA. All pairwise comparisons were made. Tukey tests were used to correct for multiple comparisons. F, Representative images (left) and quantification (right) of collagen-1-(Col-1)-stained sections from isotype or α-CD115 antibody administered mice 6 wk after sham and TAC (n=5, 4, 6, 6). Statistical significance was evaluated by a 2-way ANOVA. All pairwise comparisons were made. Tukey tests were used to correct for multiple comparisons. Scale bar=100 µm. DC indicates dendritic cells, Macs, macrophages, Mon, monocytes, NK, natural killer; PMN, polymorphonuclear leukocytes; and tSNE, t-distributed stochastic neighbor embedding. Statistical significance is summarized as ns, not significant, *P<0.05, **P<0.01, and ***P<0.001.