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Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity
C C Barnett1, E E Moore, F A Moore
1Department of Surgery, Denver General Hospital, Colo 80204, USA.
Surgery
|August 1, 1995
Summary
Upregulated intercellular adhesion molecule-1 (ICAM-1) is sufficient to cause cell damage via activated polymorphonuclear neutrophils (PMNs). This finding suggests ICAM-1 as a potential therapeutic target for PMN-mediated tissue injury.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- The interaction between CD11/CD18 on neutrophils and ICAM-1 on endothelium is crucial in neutrophil-mediated tissue injury.
- Increased ICAM-1 expression is observed in pulmonary disorders involving neutrophil inflammation.
- This study investigates if ICAM-1 upregulation alone can lead to cytotoxicity mediated by neutrophils.
Purpose of the Study:
- To determine if increased expression of ICAM-1 is sufficient to induce cytotoxicity by activated polymorphonuclear neutrophils (PMNs).
Main Methods:
- Human ICAM-1 cDNA was transfected into Chinese hamster ovarian (CHO) cells lacking inherent ICAM-1 expression.
- Flow cytometry confirmed ICAM-1 expression on 62% of transfected CHO cells.
- Cytotoxicity was assessed by measuring 51Cr release from labeled CHO cells incubated with quiescent or activated PMNs, with or without ICAM-1 blocking antibodies.
Main Results:
- Activated PMNs caused significant lysis of ICAM-1-expressing CHO cells (13.6%) compared to wild-type CHO cells (1.4%).
- Quiescent PMNs induced minimal lysis in both cell types.
- Pretreatment with an anti-ICAM-1 antibody abolished PMN-induced cytotoxicity.
Conclusions:
- Upregulation of ICAM-1 is sufficient to mediate cytotoxicity through activated PMNs.
- ICAM-1 may serve as a therapeutic target to reduce PMN-mediated damage to various cell types, including lung parenchyma.