Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.681639
Keywords
alveolar macrophage; SFTPA1; SFTPA2; SP-A1; SP-A2
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Funding
- CHILD Fund, Department of Pediatrics, Penn State University College of Medicine
- John Ardell Pursley Memorial Research Fund, Department of Pediatrics, Penn State University College of Medicine
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The human innate host defense molecules SP-A1 and SP-A2 variants have a differential impact on survival after infection in mice and lung transplant patients. SP-A interacts with alveolar macrophages and plays a role in surfactant-related aspects, potentially making it an important molecule in health and disease. The genetic complexity of SP-A can contribute to dysregulation of host defense and inflammatory processes in pulmonary diseases.
The human innate host defense molecules, SP-A1 and SP-A2 variants, differentially affect survival after infection in mice and in lung transplant patients. SP-A interacts with the sentinel innate immune cell in the alveolus, the alveolar macrophage (AM), and modulates its function and regulation. SP-A also plays a role in pulmonary surfactant-related aspects, including surfactant structure and reorganization. For most (if not all) pulmonary diseases there is a dysregulation of host defense and inflammatory processes and/or surfactant dysfunction or deficiency. Because SP-A plays a role in both of these general processes where one or both may become aberrant in pulmonary disease, SP-A stands to be an important molecule in health and disease. In humans (unlike in rodents) SP-A is encoded by two genes (SFTPA1 and SFTPA2) and each has been identified with extensive genetic and epigenetic complexity. In this review, we focus on functional, structural, and regulatory differences between the two SP-A gene-specific products, SP-A1 and SP-A2, and among their corresponding variants. We discuss the differential impact of these variants on the surfactant structure, the alveolar microenvironment, the regulation of epithelial type II miRNome, the regulation and function of the AM, the overall survival of the organism after infection, and others. Although there have been a number of reviews on SP-A, this is the first review that provides such a comprehensive account of the differences between human SP-A1 and SP-A2.
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