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Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model

¹ Dept of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, and ² Laboratory of Allergology and Pulmonary Diseases, Dept of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

CORRESPONDENCE: A. J. M. van Oosterhout, Laboratory of Allergology and Pulmonary Diseases, Dept Pathology and Laboratory Medicine, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands. Fax: 31 503610570. E-mail: A.J.M.van.Oosterhout{at}path.umcg.nl

Keywords: Allergy, interleukin-10, macrophages, regulatory T-cells, T-helper cell type 2 lymphocytes

Received: July 29, 2004
Accepted August 2, 2005

Increasing evidence suggests that macrophages (M) play a crucial downregulatory role in the initiation and progression of allergic asthma. Recently, the current authors demonstrated that ovalbumin (OVA)-loaded M (OVA-M) suppress subsequent OVA-induced airway manifestations of asthma and that this effect could be potentiated upon selective activation. In the present study, the authors further delineated the underlying pathway by which M exert this immunosuppressive effect.

To examine the migration of OVA-M, cells were labelled with 5'chloromethylfluorescein diacetate (CMFDA) and were administered (i.v.) into OVA-sensitised BALB/c mice. After 20 h, the relevant organs were dissected and analysed using fluorescent microscopy. Allergen-specificity was investigated by treating OVA-sensitised mice with keyhole limpet haemocyanin (KLH)-M activated with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN). By lengthening the period between treatment and challenge to 4 weeks it was examined whether OVA-M exerted an immunosuppressive memory response.

Strikingly, CMFDA-labelled M were not trapped in the lungs, but migrated to the spleen. ISS-ODN-stimulated KLH-M failed to suppress OVA-induced airway manifestations of asthma. Moreover, treatment with ISS-ODN-stimulated OVA-M was still effective after lengthening the period between treatment and challenge.

These data demonstrate that allergen-loaded macrophages can induce an indirect immunosuppressive response that is allergen-specific and long lasting, which are both hallmarks of a memory lymphocyte response.