title: [Changes of macrophages in colitis-associated colonic carcinogenesis].
abstract: OBJECTIVE
  To investigate the changes of quantity and phenotype of macrophages during the progress of colitis-associated carcinogenesis, and to identify the chemokines mediating macrophage recruitment.
  
  
  METHODS
  Colitis-associated cancer was induced by azoxymethane (AOM) combined with dextran sulfate sodium (DSS) in C57BL/6 mice. The three sequential developmental stages of colitis associated cancer in the mice were named AD1, AD2 and AD3, respectively. Colon tissues were collected and digested into single-cell suspension. The percentage and phenotype of macrophages in the colon tissues were determined by fluorescence activated cell sorter (FACS). Protein array and real-time polymerase chain reaction (PCR) were used to predict potential chemotatic factors of macrophages.
  
  
  RESULTS
  Colitis-associated cancer was effectively induced in C57BL/6 mice using AOM combined with DSS. The percentage of macrophages was gradually elevated in the AD1, AD2 and AD3 groups [(9.93±1.28)%, (15.42±1.15)%, (21.25±0.62)%], respectively, significantly higher than that of the control group [(2.39±0.54)%, P<0.01]. The macrophages infiltrating the colonic mucosa exhibited mainly a pro-inflammatory phenotype as CD206(-)CD86(+) MHCII(-). The positive rates of CD206 in the AD1, AD2 and AD3 groups were (15.03±1.54)%, (8.11±3.70)%, and (9.06±1.16)%, respectively, significantly lower than that of the control group [(19.43±7.31)%, P<0.01]. The positive rates of CD86 in the AD2 and AD3 groups were (46.73±6.58)% and (76.90±14.32)%, respectively, significantly higher than that of the control group [(19.37±9.69)%, P<0.01)]. The positive rates of MHCⅡ in the AD1, AD2 and AD3 groups were (31.10±2.69)%, (33.93±14.08)%, and (29.93±1.41)%, respectively, significantly lower than that of the control group [(50.30±6.58)%, P<0.01]. Protein array analysis and real-time PCR data revealed that G-CSF was the potential chemokine to recruit macrophages in the AOM-DSS mouse model.
  
  
  CONCLUSIONS
  Macrophages infiltrate increasingly during the carcinogenesis and development of colitis-associated cancer, which mostly express CD206(-)CD86(+) MHCII(-) and might be potentially recruited by G-CSF.
authors.affiliation: Department of Clinical Laboratory, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Y K
authors.initials: YK
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: W
authors.initials: W
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: J
authors.initials: J
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D001397:Azoxymethane; D063646:Carcinogenesis; D002273:Carcinogens; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002273:Carcinogens; D016179:Granulocyte Colony-Stimulating Factor; D016264:Dextran Sulfate; D001397:Azoxymethane