Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production (original) (raw)
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Journal of Histochemistry & Cytochemistry, 1992
We investigated the cellular and subcellular distribution of surfactant protein D (SPD) by immunogold l a w g in lungs of adult rats that had been given bovine s e " albumin coupled to 5-nm gold (BSAG) for 2 hr to visualize the endocytotic pathway. Specific gold labeling for SPD was found in alveolar Type II cells, Clara cells, and alveolar macrophages. In Type II cells abundant labeling was observed in the endoplasmic reticulum, whereas the Golgi complex and multivesicular bodies were labeled to a limited extent only. Lamellar bodies did not seem to contain SPD. Gold labeling in alveolar macrophages was restricted to structures containing endocytosed BSAG. In Clara ceh labeling was found in the endoplasmic reticulum, the Golgi complex, and was most 38. Tenner AJ, Robinson SL, Borchelt J, Wright JR. Human pulmonary surfactant protein A (SP-A), a protein structurally homologous to Clq, can enhance FcR-and CR1-mediated phagocytosis.
Surfactant proteins SP-A and SP-D in human health and disease
Archivum immunologiae et therapiae experimentalis
Surfactant proteins A (SP-A) and D (SP-D) are lung surfactant-associated hydrophilic proteins that have been implicated in surfactant homeostasis and pulmonary innate immunity. They are collagen-containing C-type (calcium-dependent) lectins, called collectins, and are structurally similar to mannose-binding protein of the lectin pathway of the complement system. Being carbohydrate pattern-recognition molecules, they recognize a broad spectrum of pathogens and allergens via the lectin domain, with subsequent activation of immune cells via the collagen region, thus offering protection against infection and allergenic challenge. SP-A and SP-D have been shown to be involved in viral neutralization, clearance of bacteria, fungi, and apoptotic and necrotic cells, down-regulation of allergic reaction, and resolution of inflammation. Studies on single-nucleotide polymorphism, protein levels in broncho-alveolar lavage, and gene knock-out mice have clearly indicated an association between SP-...
Non-Pulmonary Immune Functions of Surfactant Proteins A and D
Journal of innate immunity, 2017
Surfactant proteins A (SP-A) and D (SP-D) are established as essential components of our innate immune system for protecting the lung from pathogens and allergens. They essentially exert their protective functions by regulating pulmonary homeostasis. Both proteins are however widely expressed throughout the body, including the female reproductive tract, urinary tract, gastrointestinal tract, the eye, ear, nasal compartment, central nervous system, the coronary artery and the skin. The functions of SP-A and SP-D at these sites are a relatively underinvestigated area, but it is emerging that both SP-A and SP-D contribute significantly to the regulation of inflammation and protection from infection at these sites. This review presents our current understanding of the roles of SP-A and SP-D in non-pulmonary sites.
Frontiers in Immunology, 2012
A and SP-D are hydrophilic, collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens, and apoptotic cells, via C-terminal homotrimeric carbohydrate recognition domains, while the collagen region brings about the effector functions via its interaction with cell surface receptors. SPA and SP-D deal with various pathogens, using a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis, and killing mechanisms by phagocytic cells and direct growth inhibition. SPA and SP-D have also been shown to be involved in the control of pulmonary inflammation including allergy and asthma. Emerging evidence suggest that SPA and SP-D are capable of linking innate immunity with adaptive immunity that includes modulation of dendritic cell function and helper T cell polarization.This review enumerates immunological properties of SPA and SP-D inside and outside lungs and discusses their importance in human health and disease.
American Journal of Respiratory Cell and Molecular Biology, 2004
Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [Ϫ/Ϫ]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emphysema. Nitric oxide (NO) is involved in a variety of signaling processes, and because altered NO metabolism has been observed in inflammation, we hypothesized that alterations in its metabolism would underlie the proinflammatory state observed in SP-D deficiency. Examination of the bronchial alveolar lavage (BAL) from SP-D (Ϫ/Ϫ) mice reveals a significant increase in protein and phospholipid content and total cell count. NO production and inducible NO synthase expression were increased in the BAL; however, there was a decline in S-nitrosothiol (SNO) content in the BAL and a loss of SNO immunoreactivity within the tissue. This decline in SNO was accompanied by an increase in nitrotyrosine staining. We conclude that inflammation that occurs in SP-D deficiency results in an increase in NO production and a shift in the chemistry and targets of NO. We speculate that the proinflammatory response due to SP-D deficiency results, in part, from a disruption of NO-mediated signaling within the innate immune system. Surfactant protein (SP)-D is a member of a novel growing family of collagen-like lectins ("collectins") that are believed to play a role in non-antibody-mediated innate immune responses (1). SP-D shares considerable structural homology with other proteins of this type, including SPA , conglutinin, bovine collectin-43, and mannose-binding protein. SPA and SP-D are both multimeric Ca 2ϩ-binding lectins produced primarily by alveolar type II cells and nonciliated bronchiolar cells in the lung (2). In contrast to SPA , SP-D does not interact with major surfactant phospholipids and is not associated with lamellar bodies or tubular myelin. The primary function of these proteins appears to be in the modulation of host defense and inflammation, although the mechanism of their action has not been fully defined.
Immune surveillance of activated immune and tumour cells by surfactant protein D
2015
Surfactant protein D (SP-D) is a carbohydrate/charged pattern recognition molecule of the innate immune system. By virtue of its ability to recognize an array of carbohydrate patterns on the surface of a range of pathogens, SP-D can bring about opsonisation, enhanced phagocytosis and killing of a diverse range of viruses, bacteria and fungi. In addition to antimicrobial functions, which also includes bacteriostatic and fungistatic properties SP-D has also been shown to bind allergens derived from a number of sources including house dust mite, Aspergilllus fumigatus and pollen grains. SP-D allergen interaction leads to inhibition of specific IgE binding and subsequent downregulation of histamine release from sensitized basophils and mast cells. Thus, a number of murine models of pulmonary hypersensitivity and allergic asthma induced by ovalbumin, house dust mite and Aspergillus fumigatus allergens/antigens have been tested for the ability of SP-D to dampen allergic symptoms on the immunological parameters. In general, treatment of allergic models with a recombinant fragment of human SP-D (rh SP-D; composed of trimeric, neck and carbohydrate recognition domain) has been shown to cause downregualtion of specific IgE synthesis, pulmonary and peripheral eosinophilia and airway hyper reactivity, and Th2→Th1 polarisation. However, therapeutic alleviation of eosinophilia by rh SP-D treatment became evident when SP-D gene deficient mice were found to be hypereosinophilic In fact, rhSP-D binds well to eosinophils derived from allergic patients and induces apoptosis without affecting eosinophils derived from healthy individuals or nonactivated/non-sensitized eosinophils. Proteomic analysis of rh SP-D treated eosinophillic cell line that revealed that apoptosis induction takes place via p53 pathway. In this thesis, proteomic signatures were replicated using a leukemic cell line AML14.3D10 via qPCR analysis by identifying targets from a spectrum of genes, which were either upregulated or downregulated. It appears that in spite of induction of apoptosis by rh SP-D, different cells respond differentially at molecular levels (Chapter 3). Sensing that SP-D can induce apoptosis in altered or transformed cells; the effect of SP-D gene expression within pancreatic cancer cells was also investigated. The experiments confirmed p53 pathway dependence for suppression of cancer. Interestingly, factors responsible for metastasis for cancer are also downregulated by endogenous overexpression of SP-D, as validated by wound healing assay. We conclude that SP-D is a general immunosurveillance molecule, which is involved in the clearance of altered and transformed cells (Chapter 4). Chapter 5 shows a direct interaction between DC-SIGN and rh SP-D that inhibits DC-SIGN interaction of allergens and HIV-1, tow common ligands for SP-D and DC-SIGN. Using transfected human embryonic kidney (HEK) cells expressing surface DC-SIGN, we found that pre-treatment of these cells with rhSP-D suppressed DC-SIGN mediated transmission of HIV-1to co-cultured PBMCs. The effect of rhSP-D-DC-SIGN In conclusion, this
Surfactant Protein (SP)-A and SP-D as Antimicrobial and Immunotherapeutic Agents
Recent Patents on Anti-Infective Drug Discovery, 2010
Surfactant protein (SP)-A and SP-D belong to the "Soluble C-type Lectin" family of proteins and are collectively known as "Collectins". Based on their ability to recognize pathogens and to regulate the host defense, SPA and SP-D have been recently categorized as "Secretory Pathogen Recognition Receptors". SPA and SP-D were first identified in the lung; the expression of SPA and SP-D has also been observed at other mucosal surfaces, such as lacrimal glands, gastrointestinal mucosa, genitourinary epithelium and periodontal surfaces. Since the role of these proteins is not fully elucidated at other mucosal surfaces, the focus of this article is on lung-SPA and SP-D. It has become clear from research studies performed over a number of years that SPA and SP-D are critical for the maintenance of lung homeostasis and the regulation of host defense and inflammation. However, none of the surfactant preparations available for clinical use have SPA or SP-D. A review is presented here on SPA and SP-D-deficiencies in lung diseases, the importance of the administration of SPA and SP-D, and recent patents and research directions that may lead to the design of novel SPA or SP-D-based therapeutics and surfactants.
American Journal of Physiology - Lung Cellular and Molecular Physiology, 2015
Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice ( Sftpd −/−) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. β-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-β-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-β-glucan. Allergic airway disease was induced in Sftpd −/− and Sftpd +/+ mice by OVA sensitization and subsequent challenge with OVA, 1,3-β-glucan, or OVA/1,3-β-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-β-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd −/− mice, supporting previo...