Surfactant Protein A Inhibits Alveolar Macrophage Cytokine Production by a CD14 - Independent Pathway

The lung collectin surfactant protein A (SP-A) has both anti-inflammatory and pro-phagocytic activities. We and others have previously shown that SP-A inhibits the macrophage production of TNF-α stimulated by the gram negative bacterial component lipopolysaccharide (LPS). We propose that SP-A decreases the production of proinflammatory cytokines by alveolar macrophages via a CD14 independent mechanism. SP-A inhibited LPS-simulated TNF-α production in rat and mouse macrophages in the presence and absence of serum (72% and 42% inhibition, respectively). In addition, SP-A inhibited LPS-induced mRNA levels for TNF-α, IL-1α, and IL-1β as well as NF-κB DNA binding activity. SP-A also diminished ultra-pure LPS stimulated TNF-α produced by wild-type and CD14 null mouse alveolar macrophages by 58 and 88%, respectively. Additionally, SP-A inhibited TNF-α stimulated by phorbol ester myristate (PMA) in both wild-type and TLR4 mutant macrophages. These data suggest that SP-A inhibits inflammatory cytokine production in a CD14 independent manner and also by mechanisms independent of the LPS signaling pathway. LCMP-00427-2002.R1 2