Increased adhesive properties of eosinophils in sickle cell disease.
OBJECTIVE
A role for leukocytes in vasoocclusion is becoming increasingly recognized. Here we investigate a possible role for the eosinophil in sickle cell anemia (SCA).


METHODS
Eosinophils were isolated from whole blood samples of 59 steady-state SCA homozygous SS and control individuals using Percoll gradient separation, followed by immunomagnetic sorting. Adhesion of cells to FN was evaluated using static adhesion assays (60 min, 37 degrees C, 5% CO2) and eosinophil adhesion molecular expression was observed by flow cytometry.


RESULTS
SCA patients presented significantly elevated absolute eosinophil numbers. Furthermore, eosinophils isolated from these individuals demonstrated a significantly greater adhesion ( approximately 70% increased) to fibronectin (FN) than normal eosinophils in static adhesion assays. Coincubation of eosinophils with integrin-blocking monoclonal antibodies in adhesion assays showed that an association of the VLA-4, LFA-1, and Mac-1 integrins mediate the adhesion of SCA eosinophils to FN. Flow cytometry demonstrated that the expression of these integrins, however, was unaltered on the surface of SCA eosinophils, suggesting that the increased SCA eosinophil adhesion is a consequence of increased integrin affinity or avidity. SCA eosinophil adhesion to FN was further increased by the cytokine, GM-CSF, indicating that inflammation processes may further stimulate eosinophil adhesion in these patients.


CONCLUSIONS
We report that eosinophil numbers may be significantly increased in SCA individuals and that these cells appear to exist in an activated state. Such alterations may indicate a role for the eosinophil in the vasooclusive process.
Canalli
Andreia Averci
AA
Hematology and Hemotherapy Center, State University of Campinas-UNICAMP, Brazil.
Conran
Nicola
N
Fattori
André
A
Saad
Sara T O
ST
Costa
Fernando Ferreira
FF
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood*; D002448:Cell Adhesion; D018946:Chemokine CCL5 / Q000494:pharmacology; D002648:Child; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D039041:Integrin alpha4beta1 / Q000032:analysis; D016209:Interleukin-8 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged
D018946:Chemokine CCL5; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016209:Interleukin-8; D016169:Lymphocyte Function-Associated Antigen-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor