Role of Surfactant Protein-A in Nitric Oxide Production and Mycoplasma Killing in Congenic C57BL/6 Mice

Abstract

We generated congenic surfactant protein A (SP-A)-deficient (SP-A[-/-]) mice on the mycoplasma resistant C57BL/6 background (B6.SP-A[-/-]) and characterized their response to mycoplasma infection in comparison to C57BL/6 (B6) mice. B6.SP-A(-/-) mice infected with 10(6) colony-forming units (cfu) of Mycoplasma pulmonis had significantly higher bacterial lung loads than B6 mice at 72 h postinfection (p.i.). At the higher infection dose of 10(7), B6.SP-A(-/-) mice had significantly higher lung cfu at 24 h; however, no difference in mycoplasma cfu was observed between B6 and B6.SP-A(-/-) mice at 48 and 72 h p.i. We found that uninfected B6 mice had lower bronchoalveolar lavage nitrite (NO(2)(-)) and nitrate (NO(3)(-)) levels as compared with B6.SP-A(-/-) mice. On the other hand, infection of B6 mice with mycoplasmas resulted in significantly higher bronchoalveolar lavage NO(2)(-) and NO(3)(-) as compared with B6.SP-A(-/-) mice. These data indicate that SP-A may help regulate NO production in response to a specific stimulus, i.e., suppression of NO in the absence of bacteria and increased NO in the presence of bacteria. These data indicate that the contribution of SP-A to mycoplasma killing may be limited to lower doses of pathogens.

Surfactant Dysfunction in SP-A−/− and iNOS−/− Mice with Mycoplasma Infection

“…As a member of the collectin family of host defense proteins, SP-A also contributes to innate pulmonary immunity (11)(12)(13). We have previously studied M. pulmonis infection in B6 mice and showed that SP-A is necessary for maximal mycoplasma killing (4,14,15) by AM by upregulating the production of NO and reactive oxygen-nitrogen intermediates in these cells (14,15). Both SP-A Ϫ/Ϫ and iNOS Ϫ/Ϫ mice have a decreased ability to clear intratracheally instilled mycoplasmas.…”

“…C57BL/6 SP-A Ϫ/Ϫ (B6.SP-A Ϫ/Ϫ ) N10 mice were generated from 129 ϫ BS SP-A Ϫ/Ϫ mice provided by Drs. Whitsett and Korfhagen (University of Cincinnati, Ohio) (16) by backcrossing for at least 10 generations onto the B6 background (15). Mice were bred at the University of Alabama at Birmingham (UAB), and genotype was characterized from tail DNA as described previously (15).…”

“…Whitsett and Korfhagen (University of Cincinnati, Ohio) (16) by backcrossing for at least 10 generations onto the B6 background (15). Mice were bred at the University of Alabama at Birmingham (UAB), and genotype was characterized from tail DNA as described previously (15). C57BL (C57BL/6J-Nos2 tm1Lau ) transgenic mice lacking the gene for iNOS (B6.iNOS Ϫ/Ϫ ) mice were obtained from the Jackson Laboratory (Bar Harbor, ME) (14) and were bred at UAB in autoclaved microisolator cages (Lab Products, Maywood, NJ).…”

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

“…Surfactant protein A (SP-A), a 34-to 36-kDa glycoprotein, plays a major role in the modulation of innate host defense in the lung (7,16,21,41,48,52). SP-A has been shown to stimulate chemotaxis of macrophages (70), enhance phagocytosis (11,34,44,46,47,50,63), induce generation of reactive oxidants (61), regulate the nitric oxide production (1,23), and influence the proliferation of immune cells (2,38) and the production of proinflammatory cytokines (3,27,37,39,68,69). SP-A can bind to receptors on the macrophage membrane (35).…”

Significance of surfactant proteins in the diagnosis of therapeutic diseases

“…Показано, что SP-A воздействует на рост и жизнеспособность микроорга-низмов, повышая проницаемость микробной клеточной мембра-ны [3], регулирует механизмы иммунной защиты в легких путем связывания звеньев врожденного и приобретенного компонен-тов иммунитета [4], стимулирует хемотаксис макрофагов [5], вли-яет на пролиферацию клеток иммунного ответа и на продукцию провоспалительных цитокинов [6,7], повышает продукцию ре-активных оксидантов [8], регулирует продукцию оксида азота [9], стимулирует фагоцитоз [10][11][12].…”