The activation of macrophage and upregulation of CD40 costimulatory molecule in lipopolysaccharide-induced acute lung injury.
To study the activation of macrophage and upregulation of costimulatory molecule of CD40 in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) model, and to investigate the pathogenecy of ALI, mice were randomly divided into two groups. ALI model was created by injecting 0.2 mg/kg LPS in phosphate saline (PBS) in trachea. The pathologic changes of mice lungs were observed by HE staining at 24 and 48 hours after LPS treatment, then the alveolar septum damage, abnormal contraction, alveolar space hyperemia, and neutrophils or other inflammatory cells infiltration in the LPS group, but not in the control group, were observed. The expression of CD40 mRNA and CD40 protein molecules were higher in LPS group as compared to the control group by Northern blot and flow cytometry, respectively. Expression of Toll-like receptor-4 (TLR4) in activated macrophage (AMPhi) was higher in LPS group as compared to the control group by RT-PCR. The activation of NF-kappaB binding to NF-kappaB consensus oligos increased in LPS group by EMSA in macrophage. The concentrations of TNF-alpha, MIP-2, and IL-1beta cytokines from bronchoalveolar lavage fluid (BALF) were increased significantly in LPS group as compared to the control group by ELISA. The activation of AM and upregulation of costimulatory molecule CD40 induced all kinds of inflammatory cytokines releasing, then led to ALI. Therefore, both of them played vital role in the process of development of ALI.
Dong
Liang
L
Department of Pulmonary Disease, Qilu Affiliated Hospital of Shandong University, Jinan, Shandong 250012, China. ldong@medicine.bsd.uchicago.edu
Wang
Shujuan
S
Chen
Ming
M
Li
Hongjia
H
Bi
Wenxiang
W
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000276:immunology*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D019013:CD40 Antigens; D007155:Immunologic Factors; D008070:Lipopolysaccharides