SP-A preserves airway homeostasis during Mycoplasma pneumoniae infection in mice.
The lung is constantly challenged during normal breathing by a myriad of environmental irritants and infectious insults. Pulmonary host defense mechanisms maintain homeostasis between inhibition/clearance of pathogens and regulation of inflammatory responses that could injure the airway epithelium. One component of this defense mechanism, surfactant protein-A (SP-A), exerts multifunctional roles in mediating host responses to inflammatory and infectious agents. SP-A has a bacteriostatic effect on Mycoplasma pneumoniae (Mp), which occurs by binding surface disaturated phosphatidylglycerols. SP-A can also bind the Mp membrane protein, MPN372. In this study, we investigated the role of SP-A during acute phase pulmonary infection with Mp using mice deficient in SP-A. Biologic responses, inflammation, and cellular infiltration, were much greater in Mp infected SP-A(-/-) mice than wild-type mice. Likewise, physiologic responses (airway hyperresponsiveness and lung compliance) to Mp infection were more severely affected in SP-A(-/-) mice. Both Mp-induced biologic and physiologic changes were attenuated by pharmacologic inhibition of TNF-alpha. Our findings demonstrate that SP-A is vital to preserving lung homeostasis and host defense to this clinically relevant strain of Mp by curtailing inflammatory cell recruitment and limiting an overzealous TNF-alpha response.
Ledford
Julie G
JG
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Goto
Hisatsugu
H
Potts
Erin N
EN
Degan
Simone
S
Chu
Hong Wei
HW
Voelker
Dennis R
DR
Sunday
Mary E
ME
Cianciolo
George J
GJ
Foster
William M
WM
Kraft
Monica
M
Wright
Jo Rae
JR
D000818:Animals; D018893:Bronchoalveolar Lavage; D006706:Homeostasis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009177:Mycoplasma pneumoniae / Q000502:physiology*; D011019:Pneumonia, Mycoplasma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha