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. 2022 May 23;11(10):1720. doi: 10.3390/cells11101720

Figure 4.

Figure 4

Schematic representation of the contribution of peripheral blood and tissue-resident immune cells in the modulation of angiogenesis and lymphangiogenesis in COPD. Macrophages, the predominant immune cells in human lung parenchyma, release angiogenic (VEGF-A) and lymphangiogenic factors (VEGF-C, -D) [20,45,137]. Human lung macrophages also release ANGPT1 and ANGPT2 [139]. Human lung mast cells release angiogenic (VEGF-A, -B) and lymphangiogenic factors (VEGF-C, -D) [9,144,145]. Human neutrophils contain and release several angiogenic factors, including VEGF-A and ANGPT1 [46,58,156]. Human basophils contain and release VEGF-A [157]. Human eosinophils synthesize and store in their granules VEGF-A [167]. Peripheral blood monocytes release VEGF-A. VEGF-A signals mainly through the activation of VEGFR2, highly expressed in endothelial cells. VEGF-C and -D activate VEGFR3 on lymphatic endothelial cells. ANGPT1 is a Tie2 agonist, whereas ANGPT2 antagonizes ANGPT1 and VEGF-A at the Tie2 and VEGFR2, respectively.