Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics.
IL-5 and granulocyte macrophage-colony-stimulating factor (GM-CSF) are important regulators of eosinophil survival, proliferation, and effector function. To determine whether IL-5 and/or GM-CSF are generated by eosinophils at sites of allergic inflammation, we have used in situ hybridization with 35S-labeled RNA probes to study the expression of IL-5 and GM-CSF mRNA in bronchoalveolar lavage (BAL) eosinophils derived from asthmatics (n = 5) before and after endobronchial allergen challenge. Endobronchial allergen challenge induced a significant airway eosinophilia (pre-allergen challenge 0.6 +/- 0.5% eosinophilia vs post-allergen challenge 48.2 +/- 25.6% eosinophilia). Post-allergen challenge eosinophils expressed IL-5 and GM-CSF mRNA, but did not express IL-1 beta or IL-2 mRNA. To determine whether the IL-5 mRNA-positive cells coexpressed GM-CSF mRNA, double mRNA labeling experiments with a digoxigenin-11-UTP nonradioactive labeled IL-5 RNA probe and a GM-CSF 35S-labeled RNA probe were performed. These studies demonstrated that individual eosinophils expressed one of four cytokine mRNA profiles (IL-5+, GM-CSF+, 34 +/- 13%; IL-5+, GM-CSF-, 34 +/- 5%; IL-5-, GM-CSF+, 11 +/- 9%; IL-5-, GM-CSF-, 21 +/- 25%). The expression of IL-5 and GM-CSF by eosinophils at sites of allergic inflammation in asthmatics may provide an important autocrine pathway, maintaining the viability and effector function of the recruited eosinophils.
Broide
D H
DH
Department of Medicine, University of California, San Diego 92103.
Paine
M M
MM
Firestein
G S
GS
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*
D007375:Interleukin-1; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor