The interaction between different types of activated RAW 264.7 cells and macrophage inflammatory protein-1 alpha

He Zhongshi, Hui Zhang, Yang Chunxu, Zhou Yajuan, Zhou Yong, Han Guang, Xia Ling, Ouyang Wen, Zhou Fuxiang, Zhou Yunfeng, Xie Conghua

Description

Two major ways of macrophage (MΦ) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MΦ activation, which play important roles in the pathogenesis of RPI. MΦ can produce chemokine MΦ inflammatory protein-1α (MIP-1α), while MIP-1α can recruit MΦ. The difference in the chemotactic ability of MIP-1α toward distinct activated MΦ is unclear. We speculated that there has been important interaction of MIP-1α with different activated MΦ, which might contribute to the pathogenesis of RPI. Methods Classically and alternatively activated MΦ were produced by stimulating murine MΦ cell line RAW 264.7 cells with three different stimuli (LPS, IL-4 and IL-13); Then we used recombinant MIP-1α to attract two types of activated MΦ. In addition, we measured the ability of two types of activated MΦ to produce MIP-1α at the protein or mRNA level. Results Chemotactic ability of recombinant MIP-1α toward IL-13-treated MΦ was the strongest, was moderate for IL-4-treated MΦ, and was weakest for LPS-stimulated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to secrete MIP-1α was significantly stronger than that of IL-4-treated or IL-13-treated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to express MIP-1α mRNA also was stronger than that of IL-4- or IL-13-stimulated MΦ (p < 0.01). Conclusions The chemotactic ability of MIP-1α toward alternatively activated MΦ (M2) was significantly greater than that for classically activated MΦ (M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP-1α is better than that of M2. Thus, chemokine MIP-1α may play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosis in vivo , through the different chemotactic affinity for M1 and M2.

Sujets

• Macrophage

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 12
• Langue: English

Extrait

Heet al.Radiation Oncology2011,6:86 http://www.rojournal.com/content/6/1/86

R E S E A R C HOpen Access The interaction between different types of activated RAW 264.7 cells and macrophage inflammatory protein1 alpha 1,2 1,21,2 1,21,2 21 Zhongshi He, Hui Zhang, Chunxu Yang, Yajuan Zhou, Yong Zhou, Guang Han , Ling Xia , 1 11 1* Wen Ouyang , Fuxiang Zhou , Yunfeng Zhouand Conghua Xie

Abstract Background:Two major ways of macrophage (MF) activation can occur in radiationinduced pulmonary injury (RPI): classical and alternative MFactivation, which play important roles in the pathogenesis of RPI. MFcan produce chemokine MFinflammatory protein1a(MIP1a), while MIP1acan recruit MF. The difference in the chemotactic ability of MIP1atoward distinct activated MFis unclear. We speculated that there has been important interaction of MIP1awith different activated MF, which might contribute to the pathogenesis of RPI. Methods:Classically and alternatively activated MFwere produced by stimulating murine MFcell line RAW 264.7 cells with three different stimuli (LPS, IL4 and IL13); Then we used recombinant MIP1ato attract two types of activated MF. In addition, we measured the ability of two types of activated MFto produce MIP1aat the protein or mRNA level. Results:Chemotactic ability of recombinant MIP1atoward IL13treated MFwas the strongest, was moderate for IL4treated MF, and was weakest for LPSstimulated MF(p < 0.01). The ability of LPSstimulated MFto secrete MIP1awas significantly stronger than that of IL4treated or IL13treated MF(p < 0.01). The ability of LPS stimulated MFto express MIP1amRNA also was stronger than that of IL4 or IL13stimulated MF(p < 0.01). Conclusions:The chemotactic ability of MIP1atoward alternatively activated MF(M2) was significantly greater than that for classically activated MF(M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP1ais better than that of M2. Thus, chemokine MIP1amay play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosisin vivo, through the different chemotactic affinity for M1 and M2. Keywords:Macrophage, MIP1a?α?, RAW 264.7 Cells, Classically Activated, Alternatively Activated, Chemotactic Ability

Background Radiationinduced pulmonary injury (RPI) can occur during radiotherapy for thoracic cancer and limits the radiation dose that can be applied. Although the histo pathological features of RPI have been well documented, its pathogenesis has not been elucidated. Many types of inflammatory cells are involved in RPI, but pulmonary

* Correspondence: [e-mail] 1 Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169, Donghu Road, Wuchang District, Wuhan, Hubei 430071, P.R. China Full list of author information is available at the end of the article

macrophages (MF) are the most prominent [1]. Differ ent populations of activated MFcan arise in response to distinct stimuli. When stimulated by lipopolysacchar ide (LPS) and/or IFNg, the classically activated MF (M1) is generated, which secretes high levels of proin flammatory cytokines and mediators [2], and expresses inducible NO synthase (iNOS) [3]. M1 may enhance the microbicidal activity of MFand is closely associated with radiation pneumonitis. The amount of MFin the lung increases quickly after irradiation [2]. The second population of activated MFis alternatively activated MF(M2) that arises in the presence of the cytokines

© 2011 He et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.