Surfactant protein-A limits Ureaplasma-mediated lung inflammation in a murine pneumonia model.
Ureaplasma respiratory tract colonization stimulates prolonged, dysregulated inflammation in the lungs of preterm infants, contributing to bronchopulmonary dysplasia (BPD) pathogenesis. Surfactant protein-A (SP-A), a lung collectin critical for bacterial clearance and regulating inflammation, is deficient in the preterm lung. To analyze the role of SP-A in modulating Ureaplasma-mediated lung inflammation, SP-A deficient (SP-A-/-) and WT mice were inoculated intratracheally with a mouse-adapted U. parvum isolate and indices of inflammation were sequentially assessed up to 28 d postinoculation. Compared with infected WT and noninfected controls, Ureaplasma-infected SP-A-/- mice exhibited an exaggerated inflammatory response evidenced by rapid influx of neutrophils and macrophages into the lung, and higher bronchoalveolar lavage TNF-alpha, mouse analogue of human growth-related protein alpha (KC), and monocyte chemotactic factor (MCP-1) concentrations. However, nitrite generation in response to Ureaplasma infection was blunted at 24 h and Ureaplasma clearance was delayed in SP-A-/- mice compared with WT mice. Coadministration of human SP-A with the Ureaplasma inoculum to SP-A-/- mice reduced the inflammatory response, but did not improve the bacterial clearance rate. SP-A deficiency may contribute to the prolonged inflammatory response in the Ureaplasma-infected preterm lung, but other factors may contribute to the impaired Ureaplasma clearance.
Famuyide
Mobolaji E
ME
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Hasday
Jeffrey D
JD
Carter
Heather C
HC
Chesko
Kirsty L
KL
He
Ju-Ren
JR
Viscardi
Rose M
RM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D011014:Pneumonia / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D014509:Ureaplasma / Q000378:metabolism*
D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A; D009569:Nitric Oxide