title: Macrophages play an essential role in the long effects of low-dose photodynamic therapy on vessel permeability.
abstract: Low-dose photodynamic therapy (L-PDT) has been used to transiently increase the permeability of tumor vessels to improve the delivery of chemotherapeutic drugs to lung tumors. However, the effects of L-PDT in a long-term on delivery of chemotherapeutic drugs are unknown. In this study, we studied this question as well as the underlying mechanisms. We found that the effects of L-PDT on tumor vessel permeability appeared to be prolonged. Moreover, L-PDT significantly increased the number of tumor associated macrophages, and appeared to induce macrophage polarization to a M1 phenotype. Further analyses showed that L-PDT upregulated stromal cell-derived factor 1 (SDF-1) in tumor to recruit macrophages through a SDF-1/Chemokine (C-X-C Motif) Receptor 4 (CXCR4) axis, which accounted for the prolonged effects of L-PDT on vessel permeability. Application of a specific CXCR4 inhibitor significantly suppressed the L-PDT-induced macrophage recruitment, resulting in abolishment of the prolonged effects of L-PDT on vessel permeability. Furthermore, the inhibitory effects of Liporubicin™ on the growth of the implanted tumor in L-PDT-treated mice were significantly attenuated by CXCR4 inhibition. Thus, our data demonstrate a previously unappreciated long-lasting effect of L-PDT on vessel permeability, and suggest that this long-lasting effects of L-PDT treatment on vessel permeability may result from modulation of macrophage recruitment and polarization. Hence, L-PDT may be a promising method to assist chemotherapeutic approaches.
authors.affiliation: Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Surgery, the Third Affiliated Hospital of Jianghan University, 259 Baixiu Street, Wuhan 430030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Mohamed Abdulkadir
authors.initials: MA
authors.lastname: Mohamed
authors.affiliation: Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: cai.cheng@hotmail.com.
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000528:radiation effects*; D002452:Cell Count; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051379:Mice; D010778:Photochemotherapy; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4
keywords: Chemokine (C-X-C Motif) Receptor 4 (CXCR4); Chemotherapy; Low-dose photodynamic therapy (L-PDT); Macrophages; Stromal cell-derived factor 1 (SDF-1); Vessel permeability