Expression of activated Fc gamma RII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects.
BACKGROUND
Allergic asthma is associated with chronic airway and systemic immune responses. Systemic responses include priming of peripheral blood eosinophils, which is enhanced after allergen challenge. In a subpopulation of asthmatic subjects, neutrophils are associated with bronchial inflammation.


OBJECTIVE
We sought to monitor systemic granulocyte priming in allergic asthmatic subjects as a consequence of chronic and acute inflammatory signals initiated by allergen challenge.


METHODS
Blood was taken at baseline and 6 to 24 hours after allergen challenge in asthmatic subjects with and without late asthmatic responses. Systemic granulocyte priming was studied by using expression of cellular markers, such as alpha-chain of Mac-1 (alpha m)/CD11b, L-selectin/CD62L, and an activation epitope present on Fc gamma RII/CD32 recognized by monoclonal phage antibody A17.


RESULTS
Eosinophils of asthmatic subjects have a primed phenotype identified by cell-surface markers. Neutrophils of these patients were subtly primed, which was only identified after activation with N-formyl-methionyl-leucyl-phenylalanine. After allergen challenge, an acute increase in eosinophil priming characterized by enhanced expression of activated Fc gamma RII was found in patients experiencing a late asthmatic response and not in patients with a single early asthmatic response. In contrast, expression of alpha m/CD11b and L-selectin on granulocytes was not different between control and asthmatic subjects and was not affected by allergen challenge. Interestingly, expression of both adhesion molecules was positively correlated, and alpha m expression on eosinophils and neutrophils correlated positively with bronchial hyperresponsiveness.


CONCLUSIONS
Different phases, phenotypes, or both of allergic asthma are associated with distinct priming profiles of inflammatory cells in peripheral blood.


CONCLUSIONS
Insight in differences of systemic innate responses will lead to better definition of asthma subtypes and to better designs of new therapeutic options.
Kanters
Deon
D
Department of Pulmonary Diseases, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.
ten Hove
Willem
W
Luijk
Bart
B
van Aalst
Corneli
C
Schweizer
René C
RC
Lammers
Jan-Willem J
JW
Leufkens
Hubert G M
HG
Raaijmakers
Jan A M
JA
Bracke
Madelon
M
Koenderman
Leo
L
D000328:Adult; D000485:Allergens / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001435:Bacteriophages; D001769:Blood / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming; D004804:Eosinophils / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000276:immunology*
D000485:Allergens; D000911:Antibodies, Monoclonal; D000939:Epitopes; D017452:Receptors, IgG