Morphological Evidence for Novel Roles of Microtubules in Macrophage Phagocytosis

Abstract

Although the phagocytic activity of macrophages has long been studied, the involvement of microtubules in the process is not well understood. In this study, we improved the fixation protocol and revealed a dynamically rearranging microtubule network in macrophages, consisting of a basal meshwork, thick bundles at the cell edge, and astral microtubules. Some astral microtubules extended beneath the cell cortex and continued to form bundles at the cell edge. These microtubule assemblies were mutually exclusive of actin accumulation during membrane ruffling. Although the stabilization of microtubules with paclitaxel did not affect the resting stage of the macrophages, it reduced the phagocytic activity and membrane ruffling of macrophages activated with serum-MAF, which induced rapid phagocytosis. In contrast, the destabilization of microtubules with nocodazole enhanced membrane ruffling and the internalization of phagocytic targets suggesting an inhibitory effect of the microtubule network on the remodeling of the actin network. Meanwhile, the microtubule network was necessary for phagosome maturation. Our detailed analyses of cytoskeletal filaments suggest a phagocytosis control system involving Ca2+ influx, the destabilization of microtubules, and activation of actin network remodeling, followed by the translocation and acidification of phagosomes on the microtubule bundles.

Immunogenic Material Vaccine for Cancer Immunotherapy by Structure‐Dependent Immune Cell Trafficking and Modulation

“…Nocodazole can lead to microtubule instability, which in turn increases the folding of the cell membrane and internalization of phagocytic targets, and even delays the acidification and maturation of phagolysosomes. [53,54] Therefore, we speculated that RHM-AR4.5 might be internalized into BMDCs through the phagocytosis pathway.…”

Macrophage: From Recognition of Foreign Agents to Late Phagocytosis

“…However, PI [11,25] P3, the PI3K product, can stimulate Rho family GTPase activation proteins (GAPs), which inactivate GTPases and prevent actin polymerization. PI3K inhibition has also increased GTPase activation in the phagocytic cup [24,26]. PI3K activity decreases PI levels [11], P2.…”