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Published ahead of print on July 2, 2009
Am. J. Respir. Cell Mol. Biol. 2009, doi:10.1165/rcmb.2009-0016OC
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Submitted on January 12, 2009
Accepted on July 1, 2009

Macrophages: regulators of sex differences in asthma?

Barbro N. Melgert1*, Timothy B. Oriss2, Zengbiao Qi2, Barbara Dixon-McCarthy2, Marie Geerlings3, Machteld N. Hylkema3, and Anuradha Ray4

1 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States; Department of Pathology, University Medical Center Groningen, Groningen, Netherlands, 2 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States, 3 Department of Pathology, University Medical Center Groningen, Groningen, Netherlands, 4 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States; Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: b.n.melgert{at}med.umcg.nl.

Females are more susceptible to development of asthma than males. In a mouse model of ovalbumin (OVA)-induced airway inflammation, with aggravated disease in females compared to males, we studied interactions between immune and resident lung cells during asthma development to elucidate which processes are affected by sex. We studied numbers of regulatory T cells (Treg), effector T cells, myeloid dendritic cells (mDC) and alternatively activated macrophages (AAM{Phi}) and their functional capabilities. Male and female mice had comparable Treg numbers in lung tissue and comparable Treg function, but effector T cells had expanded to a greater extent in lungs of females after OVA exposure. This difference in T cell expansion was therefore not the result of lack of Treg control but appeared to be driven by a greater number of inflammatory mDC migrating from the lungs to lymph nodes in females. Resident lung cells can influence mDC migration and AAM{Phi} in lung tissue were found to be involved. Artificially elevating the number of AAM{Phi} in lung tissue increased the migration of mDC and airway inflammation. We found greater numbers of AAM{Phi} in female lungs than males, we therefore postulate that AAM{Phi} are involved in increased airway inflammation found in female mice.


Key words: Alternatively activated macrophages • myeloid dendritic cells • gender • allergy • regulatory T cells







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