LungMAP Data Explorer

Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates

Updated September 1, 2023

Malformations of or injuries to the developing lung are associated with perinatal morbidity and mortality with lifelong consequences for subsequent pulmonary health. One fetal exposure linked with poor health outcomes is chorioamnionitis, which impacts up to 25-40% of preterm births. Severe chorioamnionitis with prematurity is associated with significantly increased risk of pulmonary disease and secondary infections in childhood, suggesting that fetal inflammation may significantly alter developmental ontogeny of the lung. To test this hypothesis, we used intra-amniotic lipopolysaccharide (LPS, endotoxin) to generate experimental chorioamnionitis in prenatal Rhesus macaque (Macaca mulatta), a model which shares critical structural and temporal aspects of human lung development. Inflammatory injury directly disrupts the developing gas exchange surface of the primate lung, with extensive damage to alveolar structure, particularly the close association and coordinated differentiation of alveolar type 1 pneumocytes and specialized alveolar capillary endothelium. Single cell RNA sequencing analysis defined a multicellular alveolar signaling niche driving alveologenesis which was extensively disrupted by perinatal inflammation, leading to loss of gas exchange surface and alveolar simplification similar to that found in chronic lung disease of newborns. Blockade of IL1β and TNFα ameliorated endotoxin-induced inflammatory lung injury by blunting stromal response to inflammation and modulating innate immune activation in myeloid cells, restoring structural integrity and key signaling networks in the developing alveolus. These data provide new insight into the pathophysiology of developmental lung injury and suggest that modulating inflammation is a promising therapeutic approach to prevent fetal consequences of chorioamnionitis.

William J. ZachariasCincinnati Children's Hospital Medical
William J. Zacharias (Principle Investigator)1
1Cincinnati Children's Hospital Medical Center

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Project Label

Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates


Macaca mulatta

Sample Type


Anatomical Entity


Organ Part


Selected Cell Types


Disease Status (Specimen)


Disease Status (Donor)


Development Stage

organogenesis stage

Library Construction Method

10x 3' v3 sequencing

Nucleic Acid Source

single cell

Paired End


Analysis Protocol

75114da4-c169-4255-b577-8dc53cb8221a, f0b6a1a9-db7b-4154-b70d-8b1cca5e1785

File Format

4 file formats

Cell Count Estimate


Donor Count

fastq.gz78 file(s)h513 file(s)txt3 file(s)xlsx1 file(s)