Role of surfactant protein a and receptor SP-R210 signaling in bronchopulmonary dysplasia. - scientific abstract bronchopulmonary dysplasia (BPD) is a significant respiratory cause of morbidity and…

The National Heart, Lung, and Blood Institute awarded Pennsylvania State University (Penn State Milton S. Hershey Medical Center) $178,092 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate the role of surfactant protein A and receptor SP-R210 signaling in bronchopulmonary dysplasia.

The research addresses the pathogenesis of bronchopulmonary dysplasia (BPD), a significant respiratory cause affecting more than 15,000 premature infants annually, for which no specific treatments exist. The project will define the role of surfactant protein A (SP-A) and its macrophage receptor SP-R210 in alveolar macrophage-mediated BPD injury and elucidate mechanisms of SP-A/SP-R210-regulated intercellular crosstalk through study of extracellular vesicle uptake. Aim 1 will test whether disruption of SP-A/SP-R210 results in alveolar macrophage activation that enhances BPD in response to injury, using SP-A/SP-R210-deficient mice exposed to hyperoxia followed by lipopolysaccharide, with development of BPD and inflammation measured by histological, flow cytometry, and spatial immune cell profiling. Aim 2 will test whether disruption of SP-A/SP-R210 alters the uptake and processing of extracellular vesicles in alveolar macrophages.

Performance occurs in Hershey, Pennsylvania, with the period of performance running from September 1, 2026, through May 31, 2031. This is a project grant, the assistance type typical for investigator-initiated biomedical research under NHLBI.

Role of surfactant protein a and receptor SP-R210 signaling in bronchopulmonary dysplasia. - scientific abstract bronchopulmonary dysplasia (BPD) is a significant respiratory cause of morbidity and mortality, affecting more than 15,000 premature infants annually. Despite the substantial impact and burden of BPD on the health of society, there are no specific treatments. BPD, characterized by decreased alveolar growth, is a result of lung injury from factors such as infection, surfactant abnormalities, or oxidation stress. Limited understanding of intercellular communication in pathological states contributing to BPD development is a major knowledge GAP. Prior studies have implicated surfactant protein a (SP-a) and its macrophage receptor SP-R210 in the pathogenesis of chorioamnionitis and abnormal alveolarization. The aim of the present proposal is to define the role of the SP-a and SP-R210 in alveolar macrophages (am) mediated BPD injury. This proposal further aims to elucidate the mechanisms of SP-a/SP-R210-regulated intercellular crosstalk by studying the uptake of extracellular vesicles (EV). The rationale is that SP-a and SP-R210 modulate surfactant and immune-related endocytic functions of AMS. Importantly, conditional deletion of SP-R210 in AMS leads to BPD lung injury in transgenic mice. Based on these findings, this proposal will test the central hypothesis that the lack of SP- a/SP-R210 disrupts EV-mediated alveolarization in BPD. In aim 1, we will test the hypothesis that disruption of SP-a/SP-R210 results in am activation that enhances BPD in response to injury. To test this hypothesis, SP- a/SP-R210-deficient mice will be exposed to hyperoxia after birth, followed by LPS. Development of BPD and inflammation will be measured by histological, flow cytometry, and spatial immune cell profiling. In aim 2, we will test the hypothesis that disruption of SP-a/SP-R210 alters the uptake and processing of EVS in AMS. We will study EV uptake, and secretion of inflammatory mediators by SP-R210-deficient AMS following exposure to hyperoxia or LPS. We will use EVS isolated from human BPD patients in the presence or absence of SP-a/SP- R210 to assess differences in uptake and inflammatory mediator production by am. The ultimate impact of this research is to help design novel strategies to treat BPD and improve the health outcomes of premature infants. Furthermore, the fact that preterm neonates at risk for BPD are born with surfactant deficiency and the current standard of care- exogenous surfactant therapy lacks SP-a plus the known role of SP-a in innate immunity and survival, IT is surprising that no significant efforts have yet been made to use SP-a or SP-R210 for BPD. The contribution of this proposal is significant because this is a necessary step to move the BPD field forward in developing novel therapeutics involving SP-a and SP-R210.