Ligation of intercellular adhesion molecule 3 inhibits GM-CSF production by human eosinophils.
BACKGROUND
Intercellular adhesion molecule 3 (ICAM-3) has recently been identified on the surface of eosinophils.


OBJECTIVE
The purpose of this study was to characterize ICAM-3 expression on eosinophils in response to cytokines and to determine whether ligand binding of ICAM-3 modulates inflammatory responses of eosinophils, as it does in other leukocytes.


METHODS
To determine effects of ICAM-3 on eosinophil function, we isolated human eosinophils and used a monoclonal antibody directed against the epitope of ICAM-3 that binds to leukocyte-function antigen-1 to mimic binding of ICAM-3 and this natural ligand. We measured granulocyte-macrophage colony stimulating factor (GM-CSF) production by unstimulated eosinophils and eosinophils stimulated with ionomycin (1 micromol/L), both in the presence and absence of this anti-ICAM-3 antibody.


RESULTS
We found that 99% of eosinophils expressed ICAM-3, regardless of whether allergic symptoms were present or absent. Expression of ICAM-3 was not enhanced by proinflammatory cytokines. Expression of ICAM-3 was reduced in apoptotic cells and in cells incubated with the combination of GM-CSF and tumor necrosis factor-alpha (n = 3). Antibody binding of ICAM-3, which mimics leukocyte-function antigen-1 binding, had no effect on baseline GM-CSF production but reduced by 80% the production of GM-CSF stimulated by ionomycin (control 1969 pg/mL +/- 1259 SD versus anti-ICAM-3 396 pg/mL +/- 207 SD, n = 8) and reduced GM-CSF mRNA content.


CONCLUSIONS
ICAM-3 is highly expressed on the surface of human eosinophils, and downregulation of GM-CSF production by anti-ICAM-3 mAb suggests that ICAM-3 ligation may inhibit eosinophil inflammatory responses and survival.
Departments of Pediatrics and Medicine, University of Wisconsin Medical School, Madison, WI 53792-4108, USA.
Julie M
JM
Kessel
James E
JE
Gern
Rose F
RF
Vrtis
Julie B
JB
Sedgwick
William W
WW
Busse
D000328:Adult; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D015815:Cell Adhesion Molecules; D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D015759:Ionomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor