Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages.
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.
Mahajan
Lakshna
L
Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
Madan
Taruna
T
Kamal
Neel
N
Singh
Vijay K
VK
Sim
Robert B
RB
Telang
Shaila D
SD
Ramchand
Chaniyilparmapu N
CN
Waters
Patrick
P
Kishore
Uday
U
Sarma
P Usha
PU
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli; D005260:Female; D006801:Humans; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins; D000099192:CD69 Antigens