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BACKGROUND Interaction of the CD11/CD18 complex on polymorphonuclear neutrophils (PMNs) and intercellular adhesion molecule (ICAM)-1 on endothelium is a critical event in PMN-mediated tissue injury. In addition, increased expression of ICAM-1 on type I pneumocytes has been identified in a variety of pulmonary disorders associated with PMN-induced inflammation. We hypothesized that ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. METHODS The complementary DNA for human ICAM-1 was transfected into Chinese hamster ovarian (CHO) cells, which do not inherently express this adhesion receptor, by using the expression vector CD1.8. Fluorescence-activated cell sorter analysis revealed 62% CHO cell surface expression of ICAM-1. Wild type and transfected CHO cells were labeled with chromium 51 and exposed to quiescent or activated (1 mumol/L phorbol myristate acetate) PMNs for 4 hours. Subsets were pretreated with a monoclonal antibody to ICAM-1. PMN cytotoxicity was determined by specific percent 51Cr release. RESULTS Incubation of quiescent PMNs with wild type and transfected CHO cells produced nominal cell lysis, 0.5% +/- 0.3% and 0.2% +/- 0.2%, respectively. Activated PMNs produced 13.6% +/- 3.2% versus 1.4% +/- 0.7% cell lysis, comparing transfected with wild type CHO cells, and 0.5% +/- 0.2% cell lysis after pretreatment with a monoclonal antibody to ICAM-1, p < 0.01. CONCLUSIONS ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. This may represent a potential target for attenuating PMN-mediated injury to endothelial and other cell lines, including parenchyma.
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
June 1998,
Transplantation,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
April 1993,
Journal of neuroimmunology,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
June 2008,
Circulation research,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
January 1996,
Journal of molecular medicine (Berlin, Germany),
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
April 1998,
Shock (Augusta, Ga.),
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
February 1994,
Japanese journal of cancer research : Gann,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
April 1988,
European journal of immunology,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
September 1997,
Hepatology (Baltimore, Md.),
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
February 1999,
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery,
C C Barnett, and
E E Moore, and
F A Moore, and
W L Biffl, and
M F Smith, and
V S Carl
February 2007,
Inhalation toxicology,
