Osteopontin bridging air pollution and immunology of allergic inflammation

Ostepopontin (OPN) is a remarkable substance. The many aliases already point towards a multitude of biological functions: SPP1=secreted phosphoprotein 1, BSPI 1=bone sialoprotein-1, CIT, ETA-1, GC110940, nephropontin, osteoprotegerin, uropontin, bone sialoprotein I, early T-lymphocyte activation among others. We identified osteopontin more than 3 years ago as being upregulated in alveolar macrophages of mice exposed to ambient particles (scienceblog:doi:10.1183/09031936.06.00071205:). The immunological function with respect to allergy, however, was not so clear. Osteopontin is regulated by vitamin D response element (VDREs) where gene variants may be already associated with allergy (scienceblog:doi:10.1111/j.1399-3038.2006.00456.x:. I tried to figure out if osteopontin is a pro- or antiallergic substance but the literature on this topic was confusing. If being asked in an exam I would have said that osteopontin can activate dendritic cells and induces their differentiation toward a Th1-polarizing phenotype, relying on an earlier Blood paper (scienceblog:doi:10.1182/blood-2004-08-3228: Now a Greek paper in nature medicine has the explanation (scienceblog:doi:10.1038/nm1580:) of this conundrum

… OPNs, the secreted form of OPN, exerts opposing effects on mouse TH2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge.

So it may be possible, that vitamin D induced high OPN level lead to sensitization at the first allergen contact; while OPN might have positive effects when treating allergy at a later stage.


21.9.07 more support at PNAS and nature medicine.