Therapeutical effect of anti-CD54 antibody on septic mice

Abstract

Objective To investigated whether the anti-CD54 antibody can protect the lung function and improve the immune function on septic mice.Methods Experimental sepsis was induced by cecal ligation and puncture (CLP).24 C57BL/6 mice were randomly divided into 4 groups:Sham group,CLP group(CLP+saline),Anti-CD54 group (CLP+Anti-CD54 antibody) and Isotype group (CLP +isotype antibody).Pathological morphology changes of lung tissue were observed.Wet/dry ratios and myekoperoxidase(MPO) activities of lung tissue were measured.The expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-10 and IL-6 mRNA of lung tissue were detected by reverse transcriptive polymerase chain reaction (RT-PCR).The blood and peritoneal cavity lavage bacterial burden were assayed.The spleen and thymus were used to evaluate apoptotic level and their MPO activities were also measured.Results Compared with the CLP group and Isotype group,hematoxylin-eosin (HE) staining showed that the histological damages occurred in Anti-CD54 group were lower and expressed as interval slightly widened,no significant bleeding and a small amount of inflammatory cell infiltration.The RT-PCR results showed that the expression level of TNF-α(3.93±0.82) and IL-10 (2.83±0.55) mRNA in Anti-CD54 group were obviously lower than that of CLP group [(8.22±2.34),(6.05± 1.52)] and Isotype group [(8.54± 1.75),(5.56± 1.33)] (P＜0.05).The MPO level of thymus [(45 ± 10) U/mg],spleen [(39±8) U/mg] and lung [(64± 12) U/mg]tissue in Anti-CD54 group were lower than that of CLP group[(98±13),(78±12),(105±10) U/mg]and Isotype group[(88±20),(90±16),(110±16) U/mg] (P＜0.05).After treated with Anti-CD54 antibody (4.03 ±0.18),CLP mice lung showed lower wet-to-dry ratio compared with CLP group (4.95±0.18) and Isotype group(4.81±0.31) (P＜0.05).Compared to the CLP group[(76±18),(72 833±7 176)]and Isotype group [(69±18),(66 532±143 006)],the peritoneal cavity lavage (5±2) and blood (6±2) bacterial clearance were significantly elevated in anti-CD54 antibody group (P＜0.001).The terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assays of thymus (55±13) and spleen(45±17) in Anti-CD54 group were less than that of CLP group[(127±30),(130±25)]and Isotype group [(223±15),(110±42)](P＜0.01)respectively.Conclusions Anti-CD54 antibody showed therapeutic effects on septic mice,which may be related to improving pulmonary function,increasing blood and peritoneal clearance and inhibition of apoptosis of spleen and thymus. Key words: Sepsis; Cecal ligation and puncture; Neutrophil; Intercellular adhesion molecule-1; Immune function