title: Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.
abstract: 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.
authors.affiliation: Department of Surgery, Denver General Hospital, Colo 80204, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Barnett
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: F A
authors.initials: FA
authors.lastname: Moore
authors.forename: W L
authors.initials: WL
authors.lastname: Biffl
authors.forename: M F
authors.initials: MF
authors.lastname: Smith
authors.forename: V S
authors.initials: VS
authors.lastname: Carl
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D014162:Transfection
chemical_list: D018799:Intercellular Adhesion Molecule-1