Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.
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.
Barnett
C C
CC
Department of Surgery, Denver General Hospital, Colo 80204, USA.
Moore
E E
EE
Moore
F A
FA
Biffl
W L
WL
Smith
M F
MF
Carl
V S
VS
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
D018799:Intercellular Adhesion Molecule-1