International Immunology Advance Access published online on July 14, 2008
International Immunology, doi:10.1093/intimm/dxn058
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Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages
1 Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
2 Department of Biochemistry, M.S. University of Baroda, 390 002 Vadodara, India
3 Centre for Visceral Mechanisms, V.P. Chest Institute, University of Delhi, 110007 Delhi, India
4 MRC Immunochemistry Unit, South Parks Road, Oxford OX1 3QU, UK
5 Kemin Nutritional Technologies (India) Pvt. Ltd., The Trapezium, No.39, IInd floor, Nelson Manickamrd, Chennai 600 029, India
6 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
7 CCCB/Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge Campus, West London UB8 3PH, UK
8 Plant Pathology Division, Indian Agriculture Research Institute, Pusa, New Delhi 110012, India
Correspondence to: Correspondence to: T. Madan; E-mail: taruna_m{at}hotmail.com
Pulmonary surfactant protein-D (SP-D) is a multifunctional, pattern recognition molecule involved in resistance to allergen challenge and pulmonary inflammation. In view of therapeutic effects of exogenous SP-D or recombinant fragment of human surfactant protein-D (rhSP-D) (composed of eight Gly-X-Y collagen repeat sequences, homotrimeric neck and lectin domains) in murine models of lung allergy and hypereosinophilic SP-D gene-deficient mice, we investigated the possibility of a direct interaction of purified rhSP-D with human eosinophils derived from allergic patients and healthy donors. rhSP-D showed a sugar- and calcium-dependent binding to human eosinophils, suggesting involvement of its carbohydrate recognition domain. While eosinophils from allergic patients showed a significant increase in apoptosis, oxidative burst and CD69 expression in presence of rhSP-D, eosinophils from healthy donors showed no significant change. However, these eosinophils from healthy donors when primed with IL-5 exhibited increase in apoptosis on incubation with rhSP-D. Apoptosis mediated by rhSP-D in primed eosinophils was not affected by the antioxidant, N-acetyl-L-cysteine. There was a manifold increase in binding of rhSP-D to apoptotic eosinophils than the normal eosinophils and rhSP-D induced a significant increase in uptake of apoptotic eosinophils by J774A.1 macrophage cells. The study suggests that rhSP-D mediated preferential increase of apoptosis of primed eosinophils while not affecting the normal eosinophils and increased phagocytosis of apoptotic eosinophils may be important mechanisms of rhSP-D and plausibly SP-D-mediated resolution of allergic eosinophilic inflammation in vivo.
Keywords: allergy, apoptosis, eosinophils, phagocytosis
Transmitting editor: H. Karasuyama
Received 3 May 2007, accepted 16 May 2008.