Effect of surfactant protein A (SP-A) on the production of cytokines by human pulmonary macrophages

Surfactant protein A (SP-A) is thought to play a role in the modulation of lung inflammation during acute respiratory distress syndrome (ARDS). However, SP-A has been reported both to stimulate and to inhibit the proinflammatory activity of pulmonary macrophages (M phi). Because of the interspecies differences and heterogeneity of M phi subpopulations used may have influenced previous controversial results, in this study, we investigated the effect of human SP-A on the production of cytokines and other inflammatory mediators by two well-defined subpopulations of human pulmonary Mb. Surfactant and both alveolar (aM phi) and interstitial (iM phi) macrophages were obtained from multiple organ donor lungs by bronchoalveolar lavage and enzymatic digestion. Donors with either recent history of tobacco smoking, more than 72 h on mechanical ventilation, or any radiological pulmonary infiltrate were discarded. SP-A was purified from isolated surfactant using sequential butanol and octyl glucoside extractions. After 24-h preculture, purified M phi were cultured for 24 h in the presence or absence of LPS (10 mug/mL), SP-A (50 mug/mL), and combinations. Nitric oxide and carbon monoxide (CO) generation (pmol/mug protein), cell cGMP content (pmol/mug protein), and tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1, and IL-6 release to the medium (pg/mug protein) were determined. SP-A inhibited the lipopolysaccharide (LPS)-induced TNFa: response of both interstitial and alveolar human M phi, as well as the IL-l response in iM phi. The SP-A effect on TNF alpha production could be mediated by a suppression in the LPS-induced increase in intracellular cGMP. In iM phi but not in aM phi, SP-A also inhibited the LPS-induced IL-1 secretion and CO generation. These data lend further credit to a physiological function of SP-A in regulating alveolar host defense and inflammation by suggesting a fundamental role of this apoprotein in limiting excessive proinflammatory cytokine release in pulmonary M phi during ARDS.