RESUMEN
Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer prevention.
Asunto(s)
Adenocarcinoma/inmunología , Apoptosis/inmunología , Carcinogénesis/inmunología , Neoplasias Pulmonares/inmunología , Macrófagos/inmunología , Neovascularización Patológica/inmunología , Adenocarcinoma/inducido químicamente , Adenocarcinoma del Pulmón , Animales , Autofagia/inmunología , Benzofuranos/farmacología , Permeabilidad Capilar/fisiología , Carcinogénesis/inducido químicamente , Carcinoma Pulmonar de Lewis , Diferenciación Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Embrión de Pollo , Cloroquina/farmacología , Ácido Clodrónico/farmacología , Medios de Cultivo Condicionados/farmacología , Células Endoteliales , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/inducido químicamente , Ratones , Ratones Endogámicos C57BL , Proteínas Asociadas a Microtúbulos/biosíntesis , Fosfoproteínas/biosíntesis , Transactivadores/biosíntesis , Uretano/farmacologíaRESUMEN
The airflow striking sampling was compared with flat utensils sedimentation sampling for collection of air microorganisms. The result showed that air microorganism count with the former method is more efficient than the latter method (P < 0.05). The flat utensils sedimentation sampling only collected larger particles of microorganism so the air microorganism count was not accurate. However, it is still a suitable method in hygiene without other choices. The airflow striking sampling collected more middle and tiny particles for air microorganism than the sedimentation sampling and can accurately show microorganism content in air, so it is an optimal sampling method.