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). Howeve r, SP-A has been reported both to stimulate and to inhibit the proinflammat ory activity of pulmonary macrophages (M phi). Because of the interspecies differences and heterogeneity of M phi subpopulations used may have influen ced previous controversial results, in this study, we investigated the effe ct of human SP-A on the production of cytokines and other inflammatory medi ators by two well-defined subpopulations of human pulmonary Mb. Surfactant and both alveolar (aM phi) and interstitial (iM phi) macrophages were obtai ned 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 w ere 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), S P-A (50 mug/mL), and combinations. Nitric oxide and carbon monoxide (CO) ge neration (pmol/mug protein), cell cGMP content (pmol/mug protein), and tumo r necrosis factor alpha (TNF alpha), interleukin (IL)-1, and IL-6 release t o the medium (pg/mug protein) were determined. SP-A inhibited the lipopolys accharide (LPS)-induced TNFa: response of both interstitial and alveolar hu man M phi, as well as the IL-l response in iM phi. The SP-A effect on TNF a lpha production could be mediated by a suppression in the LPS-induced incre ase 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 defe nse and inflammation by suggesting a fundamental role of this apoprotein in limiting excessive proinflammatory cytokine release in pulmonary M phi dur ing ARDS.