Distinct Effects of Surfactant Protein A or D Deficiency During Bacterial Infection on the Lung

Abstract

Mice lacking surfactant protein (SP)-A (SP-A−/−) or SP-D (SP-D−/−) and wild-type mice were infected with group B streptococcus or Haemophilus influenzae by intratracheal instillation. Although decreased killing of group B streptococcus and H. influenzae was observed in SP-A−/− mice but not in SP-D−/− mice, deficiency of either SP-A or SP-D was associated with increased inflammation and inflammatory cell recruitment in the lung after infection. Deficient uptake of bacteria by alveolar macrophages was observed in both SP-A- and SP-D-deficient mice. Isolated alveolar macrophages from SP-A−/− mice generated significantly less, whereas those from SP-D−/− mice generated significantly greater superoxide and hydrogen peroxide compared with wild-type alveolar macrophages. In SP-D−/− mice, bacterial killing was associated with increased lung inflammation, increased oxidant production, and decreased macrophage phagocytosis. In contrast, in the absence of SP-A, bacterial killing was decreased and associated with increased lung inflammation, decreased oxidant production, and decreased macrophage phagocytosis. Increased oxidant production likely contributes to effective bacterial killing in the lungs of SP-D−/− mice. The collectins, SP-A and SP-D, play distinct roles during bacterial infection of the lung.

Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants

“…[29][30][31] Plasma levels and functional activity of the collectins are known to be determined by polymorphisms in exon 1 and in the promotor region of the MBL2 gene, and thus a genetic susceptibility to the development of severe infections has been suggested as genetic variants associated with low MBL concentrations revealed a clinical phenotype. 3,[7][8][9][10] Preterm infants, known to exhibit a markedly increased risk for the development of severe infections, may critically depend on their innate immune response, as the presence of early-onset and nosocomial infections mainly determines acute and long-term morbidity and mortality in this population, especially regarding the development of neurological and pulmonary impairment.…”

Significance of surfactant proteins in the diagnosis of therapeutic diseases

“…SP-D связывается с грамотрицательными бактериями, такими как Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli и Haemophilus influenzaе, способствуя их агглютинации и стимуляции хемотак-сиса нейтрофилов, макрофагов и эозинофилов к месту инвазии патогена [25][26][27]. SP-D также может связываться с грамположи-тельными бактериями, такими как Streptococcus pneumoniae и Stafylococcus aureus, а также с микобактериями [28,29], респира-торно-синцитиальным вирусом, вирусом гриппа [30], грибами Pneumocystis carinii, Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans [31].…”

“…SP-A (-/-) мыши проявляли повышенную чувстви-тельность к ряду патогенных микроорганизмов, включая группу Streptococcus [35], P aeruginosa [36], H. influenza [27], P carinii [37,38], K. pneumonia [34]. SP-D (-/-) мыши более восприимчивы к инфекциям дыхательных путей, вызываемым вирусом гриппа [17], респираторно-синцитиальным вирусом [28].…”

Exogenous surfactant instillation attenuates inflammatory response to acid-induced lung injury in rat

“…Surfactant blocks lipopolysaccharide (LPS) signaling and inhibits proinflammatory cytokine secretion in human alveolar macrophages [12,13], and deficiency of surfactant protein increases the inflammatory response to LPS in vitro [14,15]. Several experimental and clinical studies indicated that surfactant proteins attenuate acute lung injury and/or production of inflammatory cytokines in the lungs [16][17][18][19][20].…”