Human eosinophils migrate across an intestinal epithelium in response to platelet-activating factor.
OBJECTIVE
Transmigration of eosinophils across intestinal epithelia occurs in a variety of mucosal inflammatory disorders and results in the formation of crypt abscesses containing eosinophils. However, the conditions required to drive transepithelial migration of eosinophils are not understood.


METHODS
This study investigated eosinophil migration across intestinal epithelia using purified eosinophils and confluent monolayers of the human intestinal epithelial cell line T84.


RESULTS
Unactivated eosinophils (i.e., no granulocyte/macrophage colony-stimulating factor [GM-CSF] preexposure) did not migrate across T84 monolayers in the presence of transepithelial gradients of C5a, n-formyl-methionyl-leucyl-phenylalanine (fMLP), or platelet-activating factor (PAF). In contrast, activation of eosinophils by coincubation or pretreatment with GM-CSF enabled transepithelial migration in response to PAF but not to C5a or fMLP gradients in a time- and dose-dependent fashion. Specificity was confirmed by both the PAF receptor antagonist WEB-2086 and the PAF enantiomer 2-lyso-beta-acetyl-gamma-O-hexadecyl. Finally, addition of functionally inhibitory monoclonal antibodies to CD11b but not CD11a, very late activation antigen (VLA-4), or intracellular adhesion molecule 1 inhibited eosinophil migration.


CONCLUSIONS
These studies establish that physiologically directed migration of eosinophils across model epithelia occurs but that this process is governed by the state of eosinophil activation, the specific chemotactic gradient imposed, and the availability of specific surface integrins to participate in putative eosinophil-epithelial adhesion steps.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
M B
MB
Resnick
S P
SP
Colgan
C A
CA
Parkos
C
C
Delp-Archer
D
D
McGuirk
P F
PF
Weller
J L
JL
Madara
D000328:Adult; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007422:Intestines; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013997:Time Factors
D015815:Cell Adhesion Molecules; D010972:Platelet Activating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor