Figure 5. Histamine deficiency impairs macrophage infiltration and suppresses the healing process.

(a) 1d post MI, FACS data showed that HDC^−/− mice had a significantly lower percentage of CD11b⁺Ly6C⁺ total macrophages in the infarcted heart than the WT counterparts (WT: 15.72 ± 1.72% vs HDC^−/−:4.22 ± 0.39%, ***p < 0.001; n = 10–12). 7d post MI, the percentage of macrophages in the infarcted heart of WT mice declined, but in HDC^−/− mice it still went up and even exceeded that of WT mice (*p < 0.05 vs WT; n = 5–7). These effects could be abrogated by exogenous histamine (His) injection (**p < 0.01 vs HDC^−/−, *p < 0.05 vs HDC^−/−; n = 6–9). (b) As for CD11b⁺Ly6C^high M1 macrophages, the similar trend was observed. (c,d) Representative images of anti-CD68 immunohistochemistry study in the hearts 1d ((c) scale bar = 50 μm) and 7d ((d) scale bar = 50 μm) post MI. The trends were consistence with that in FACS data. (e,f) 3d post MI, dead cardiomyocytes were almost completely replaced by granulation tissue in WT mice ((e), HE staining, scale bar = 50 μm). In contrast, at the same time point, HDC^−/− mice showed incomplete granulation tissue formation and persistent presence of injured cardiomyocytes in the infarct ((f), HE staining, scale bar = 50 μm).