Intercellular adhesion molecule-1 in human corneal endothelium. Modulation and function.
The endothelium lining the posterior corneal surface performs physiologic pump functions essential to corneal clarity and integrity. A hallmark of keratitis, anterior ocular inflammation, and corneal allograft rejection is leukocyte adherence to the corneal endothelium (CE) forming keratitic precipitates. To elucidate mechanisms governing cornea-leukocyte interactions, cultured human CE cells and intact corneas were examined for expression of intercellular adhesion molecule-1 (ICAM-1), which binds the lymphocyte function-associated antigen-1 (LFA-1) on all leukocytes and enhances delayed-type hypersensitivity mediated by class II major histocompatibility complex antigens. Immunohistochemistry on culture CE cells using monoclonal anti-ICAM-1 antibody yield positive staining that increased after exposure to interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (gamma-IFN). Standard leukocyte adherence assays demonstrated ICAM-1-mediated CE-neutrophil binding, which was specifically blocked by antibody to ICAM-1 or antibodies to LFA-1 on neutrophils. In whole human corneas, gamma-IFN increased CE and stromal keratocyte ICAM-1 immunoreactivity and enhanced CE-neutrophil adherence. As in CE cell cultures, antibody to ICAM-1 effectively blocked neutrophil binding to the CE cells of whole corneas. These results are the first to demonstrate ICAM-1 in ocular tissue. They indicate that CE cells express functional ICAM-1, which may be modulated by inflammatory cytokines, ICAM-1 provides mechanisms for keratitic precipitate formation, regulation of corneal leukocyte trafficking and the generation of immune responses that may be crucial to allograft rejection.
Elner
V M
VM
Department of Ophthalmology (Kellogg Eye Center), University of Michigan, Ann Arbor 48105.
Elner
S G
SG
Pavilack
M A
MA
Todd
R F
RF
Yue
B Y
BY
Huber
A R
AR
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002675:Child, Preschool; D004728:Endothelium, Corneal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D013194:Staining and Labeling; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1