CD11c항체가 Lipopolysaccharide에 의한 국소적 Shwartzman 반응의 유발에 미치는 영향 = Effects of Anti-CD11c Antibody on Induction of Localized Shwartzman Reaction with Lipopolysaccharide

다국어 초록 (Multilingual Abstract)

Lipopolysaccharide(LPS), a component of the cell walls of gram negative bacilli, may induce sepsis, disseminated intravascular coagulation, and multisystem organ failures. The, Shwartzman reaction is an experimental model of LPS-inducing inflammation with localized or generalized intravascular coagulation. This study was carried out to investigate the effects of CD11/CD18 blocking with anti-CD11c antibody on induction of the localized Shwartzman reaction.
The control group consisted of mice subcutaneously injected with E.coli LPS(0.01mg). The experimental groups were divided into two subgroups: One consisted of the mice intraperitoneally injected with LPS(2.5mg/kg) with a 24 hour interval after subcutaneous injection with LPS. The other group consisted of mice intraperitoneally injected with LPS with a 24 hour interval after intradermal injection with LPS and with pretreatment of anti-CD11c antibody(20ug). The mice were sacrificed at 24 hours after the final injection. The skins were observed by light and electron microscopy. TNF-α mRNA expression of the experimental group was determined by RTPCR.
With light microscopy. the skin of the control group revealed moderate infiltration of neutrophils and monocytes in the dermis.
The experimental group injected with LPS in the subcutaneous and intrap:ritoneal areas demonstrated diffuse and heavy infiltration of neutrophils and monocytes with focal necrosis and hemorrhage in the dermis. These findings were consistent with the Shwartzman reaction. The mice subcutaneously and intraperitoneally injected LPS with pretreatment of anti-CD11c antibody showed moderate infiltration of neutrophils and monocytes in the dermis without hemorrhage and necrosis.
With electron microscopy, the control group showed the accumulation of a fine granular substance, as seen in edema, and infiltration of neutrophils and monocytes. The capillaries revealed mild endothelial edema without fibrin thrombi formation.
In the experimental groups, the mice with the induced Shwartzman reaction demonstrated necrotic inflammatory cell debris and accumulation of edema fluid substance in dermal tissues. The capillaries showed swelling, separation and denudation of endothelial cells with formation of microthrombi composed of fibrin and platelets. However, the anti-CD11c antibody pretreated experimental group showed intradermal infiltration of neutrophils and monocytes and edema without necrosis or microthrombi. On RT-PCR, TNF-a mRNA was definitely expressed in dermal tissues of Shwartzman reaction-induced group but was not in anti-CD11c antibody-pretreated group.
According to the above results, it can be concluded that the CD11c/CD18 is a LPS receptor and that the LPS-induced Shwartzman reaction is effectively suppressed with the anti-CDllc antibody.