{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSurfactant protein A1 (SP-A1), encoded by the SFTPA1 gene, is an essential collectin produced predominantly by alveolar type II cells that underpins lung innate immunity. SP-A1 participates in the maintenance and proper assembly of pulmonary surfactant while directly interacting with microbial ligands and cell‐surface receptors on alveolar macrophages to modulate inflammatory responses and promote pathogen clearance. In humans, the existence of two SP-A genes (SFTPA1 and SFTPA2) results in structurally similar but functionally nonredundant proteins, with SP-A1 contributing uniquely to the regulation of surfactant homeostasis and immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and biochemical studies have revealed that allelic variations and mutations within SFTPA1 can markedly affect SP-A1’s secretion, oligomerization, and stability. For example, a germline missense mutation (p.Trp211Arg) in SFTPA1 was shown to impair SP-A1 secretion and is associated with a spectrum of lung diseases—including idiopathic pulmonary fibrosis and lung adenocarcinoma—thus underscoring the protein’s protective role in alveolar homeostasis. In addition, comparative analyses between SP-A1 and SP-A2 have demonstrated that differences in supratrimeric assembly and collagen domain stability are critical determinants that alter ligand aggregation and receptor‐mediated signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, SP-A1–derived proteins exhibit distinct immunomodulatory properties compared with their SP-A2 counterparts. In vitro studies using expressed human SP-A variants have demonstrated that SP-A1 generally provides a lower enhancement of alveolar macrophage–mediated phagocytosis relative to SP-A2, and specific SFTPA1 polymorphisms have been linked with altered susceptibility to infectious diseases such as tuberculosis. These findings collectively highlight that subtle variations in SFTPA1 structure not only modulate biophysical characteristics—such as ligand binding and aggregation—but also have far‐reaching effects on host–pathogen interactions and the individual risk for lung disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frederico Vieira, Johannes W Kung, Faizah Bhatti "}, {"type": "b", "children": [{"type": "t", "text": "Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Anat (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.aanat.2017.03.002"}], "href": "https://doi.org/10.1016/j.aanat.2017.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28351530"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28351530"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Moises Selman, Hung-Mo Lin, Martha Montaño, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw014"}], "href": "https://doi.org/10.1093/hmg/ddw014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26792177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26792177"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "I García-Verdugo, G Wang, J Floros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural analysis and lipid-binding properties of recombinant human surfactant protein a derived from one or both genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi026540l"}], "href": "https://doi.org/10.1021/bi026540l"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12437362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12437362"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meri Rova, Ritva Haataja, Riitta Marttila, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Data mining and multiparameter analysis of lung surfactant protein genes in bronchopulmonary dysplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh132"}], "href": "https://doi.org/10.1093/hmg/ddh132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15102713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15102713"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "S Malik, C M T Greenwood, T Eguale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants of the SFTPA1 and SFTPA2 genes and susceptibility to tuberculosis in Ethiopia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-005-0092-y"}], "href": "https://doi.org/10.1007/s00439-005-0092-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16292672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16292672"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anatoly N Mikerov, Todd M Umstead, Weixiong Huang, et al. 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