A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation.
BACKGROUND
In human blood basophils, cross-linking the high-affinity IgE receptor Fc epsilonRI with multivalent antigen activates a signaling pathway leading to secretion of inflammatory mediators and cytokine production. Basophils are known to play an important role in the pathogenesis of asthma but there has been no comprehensive examination of the effectors these cells produce. Here a study of the transcription and release of a selection of chemokines and cytokines from basophils was undertaken.


METHODS
A Cartesian antibody array provided an effective method of assaying for multiple cytokines and chemokines simultaneously. Results were verified by RT-PCR and ELISA assays. This allowed the comparison of freshly prepared peripheral blood basophil responses to cross-linking of the high-affinity IgE receptor, with and without preincubation with IL-3.


RESULTS
Evidence that human blood basophils produce the chemokines MIP-5, eotaxin and GM-CSF was provided by antibody array and RT-PCR analyses. Preincubation with IL-3 enhanced the expression and release of IL-13, IL-8 and mRNA transcripts encoding MIP-5 and GATA2 in basophils from both asthmatic and control subjects. Leptin mRNA transcription, storage and release in basophils are described for the first time.


CONCLUSIONS
Surveying cytokine and chemokines stored and released by peripheral blood basophils shows that asthmatic and control subjects share similar profiles even when their degranulation responses are distinct. Evidence is provided for the production of leptin, GM-CSF, eotaxin and MIP-5 by peripheral blood basophils. IL-3 preincubation enhances the production and release of IL-8 upon IgE receptor cross-linking.
Gilmartin
Laura
L
Department of Pathology, University of New Mexico, Albuquerque, N. Mex. 87131, USA.
Tarleton
Christy A
CA
Schuyler
Mark
M
Wilson
Bridget S
BS
Oliver
Janet M
JM
D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D050989:GATA2 Transcription Factor / Q000032:analysis / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D018793:Interleukin-13 / Q000032:analysis / Q000096:biosynthesis; D007377:Interleukin-3 / Q000494:pharmacology; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D020738:Leptin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C108814:CCL15 protein, human; D019742:Chemokines, CC; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; D007377:Interleukin-3; D016209:Interleukin-8; D020738:Leptin; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor