alergia

Pesquisadores publicaram, recentemente, no Mechanisms of Asthma and Allergic Inflammation, um estudo em que monitorizaram a cinética do priming de eosinófilos no sangue periférico e em fluído de lavado broncoalveolar de pacientes portadores de asma alérgica antes e após broncoprovocação com alérgeno.

Priming de eosinófilos sangüíneos obtidos de pacientes portadores de alergia e de doadores sem alergia foi medido através de marcação por anticorpos monoclonais com fagos A17 e A27 que reconhecem epitopos associados ao priming em fagócitos. Além disso, eosinófilos recuperados de lavado broncoalveolar e do sangue de pacientes com alergia após provocação pulmonar segmentar e total foram semelhantemente analisados.

Os pesquisadores encontraram upregulation de epitopos associados a priming, dose-dependente, induzida por citocinas. Pacientes portadores de asma alérgica apresentaram fenótipo de eosinófilos que sofreram priming parcial in vivo, posteriormente submetidos a priming in vitro após incubação com citocinas e quimiocinas. Priming estava aumentado no sangue periférico 6 horas após provocação total do pulmão, bem como após provocação segmentar pulmonar com alérgeno. Interessantemente, eosinófilos obtidos do lavado broncoalveolar 48 horas após provocação segmentar com alérgeno exibiram maior fenótipo submetido a priming.

Portanto, os pesquisadores concluíram que reações inflamatórias alérgicas locais induzem priming parcial de eosinófilos sistêmicos no sangue periférico. Eosinófilos encontrados nas vias aéreas são altamente submetidos a priming, consistente com a capacidade inflamatória marcadamente estimulada observada nestas células.

Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge - American Academy of Allergy, Asthma and Immunology - May 2005 • Volume 115 • Number 5

May 2005 • Volume 115 • Number 5

Mechanisms of Asthma and Allergic Inflammation
Gradual increase in priming of human eosinophils during extravasation from peripheral blood to the airways in response to allergen challenge

Bart Luijk, MD a [MEDLINE LOOKUP] Caroline A. Lindemans, MD a [MEDLINE LOOKUP] Deon Kanters, BSc a [MEDLINE LOOKUP] Roos van der Heijde, MD, PhD a [MEDLINE LOOKUP] Paul Bertics, PhD b [MEDLINE LOOKUP] Jan-Willem J. Lammers, MD, PhD a [MEDLINE LOOKUP] Mary-Ellen Bates, PhD b [MEDLINE LOOKUP] Leo Koenderman, PhD a * [MEDLINE LOOKUP]

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Abstract

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Background Eosinophils isolated from the blood of patients with allergic asthma exhibit enhanced responsiveness to multiple stimuli compared with cells from normal controls, a phenomenon generally referred to as priming. This priming response is essential for optimal activation with augmented responses including chemotaxis, cytotoxicity, respiratory burst, and the release of proinflammatory lipid mediators.

Objective To monitor the kinetics of priming of eosinophils in the peripheral blood and in the bronchoalveolar lavage fluid of patients with allergic asthma before and after allergen challenge.

Methods Priming of blood eosinophils obtained from patients with allergy and donors without allergy was measured by labeling with monoclonal phage antibodies A17 and A27 recognizing priming-associated epitopes on phagocytes. In addition, blood and bronchoalveolar lavage fluid eosinophils from subjects with allergy after segmental and whole lung allergen challenge were similarly analyzed.

Results A dose-dependent cytokine-induced upregulation of priming-associated epitopes on blood eosinophils was found. Patients with allergic asthma exhibited an in vivo partially primed eosinophil phenotype, which is further primed in vitro after cytokine or chemokine incubation. Priming was increased in peripheral blood 6 hours after whole lung challenge as well as after segmental allergen challenge. Interestingly, eosinophils obtained from the bronchoalveolar lavage fluid 48 hours after segmental allergen challenge exhibited a higher primed phenotype.

Conclusion These data are consistent with a model in which local allergic inflammatory reactions induce partial systemic eosinophil priming in the peripheral blood. Eosinophils found in the airway are highly primed, consistent with the markedly upregulated inflammatory capacity observed in these cells.

Publishing and Reprint Information

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• ^aFrom the Department of Pulmonary Diseases, University Medical Center, Utrecht
• ^bDepartment of Biomolecular Chemistry, University of Wisconsin
• Supported by a research grant of GlaxoWellcome and the Netherlands Asthma Foundation project numbers 3.2.99.16, 3.2.98.40, and 3.2.01.49. Additional funding was provided by National Institutes of Health grant MO RR03186 to the University of Wisconsin General Clinical Research Center and SCOR grant HL56396 P50 to Dr Bertics.
• ^*Reprint requests: Leo Koenderman, PhD, Department of Pulmonary Diseases, University Medical Center, Heidelberglaan 100, NL 3584 CX Utrecht, The Netherlands.
• Email address: L.Koenderman@hli.azu.nl (Leo Koenderman)
• Utrecht, The Netherlands, and Madison, Wis
• Submitted July 29, 2004.
• Revision submitted February 2, 2005.
• Accepted February 4, 2005.
• Copyright © 2005 by American Academy of Allergy, Asthma and Immunology
• doi: 10.1016/j.jaci.2005.02.002