Abstract
BackgroundTwo 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.MethodsClassically 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.ResultsChemotactic 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).ConclusionsThe 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.
Highlights
Two major ways of macrophage (MF) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MF activation, which play important roles in the pathogenesis of RPI
Macrophage culture The murine MF cell line RAW 264.7 was obtained from the China Center for Type Culture Collection (CCTCC) at Wuhan University, and grown in DMEM supplemented with 10% heated-inactivated FCS, 2 mmol/L L-glutamine, and 100 U/mL penicillin/streptomycin (GIBCO) at 37oC in a humidified incubator of 5% CO2
Expression of macrophage enzyme activity To obtain activated states of MF, MF was stimulated by LPS, IL-4, and IL-13, and the activated states were evaluated by measuring inducible NO synthase (iNOS) and arginase activity
Summary
Two major ways of macrophage (MF) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MF activation, which play important roles in the pathogenesis of RPI. The difference in the chemotactic ability of MIP-1a toward distinct activated MF is unclear. We speculated that there has been important interaction of MIP-1a with different activated MF, which might contribute to the pathogenesis of RPI. Radiation-induced pulmonary injury (RPI) can occur during radiotherapy for thoracic cancer and limits the radiation dose that can be applied. The histopathological features of RPI have been well documented, its pathogenesis has not been elucidated. Many types of inflammatory cells are involved in RPI, but pulmonary. Arginase 1 can contribute to the production of ECM by catalyzing the formation of polyamines and collagen, overexpression of which improves pulmonary fibrosis. Excessive IL-4 and the related M2 have been observed in radiation pulmonary fibrosis (RPF) [2]
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