Rat Surfactant Apoprotein A (SP-A) Exhibits Antioxidant Effects on Alveolar Macrophages

Abstract

The effects of surfactant apoprotein A (SP-A) on the superoxide production of rat alveolar macrophages (AM) were studied. Superoxide production was measured by the ferricytochrome c reduction method. When AM were incubated with SP-A only during the measurement of superoxide production, superoxide production was not influenced by SP-A. However, when AM were preincubated with SP-A at a concentration of 1, 2, and 10 micrograms/ml, superoxide production by AM was significantly inhibited (P < 0.05, P < 0.01, P < 0.01, respectively). The superoxide production of AM stimulated by PMA was significantly inhibited by SP-A at a concentration of 1 microgram/ml (P < 0.01), and superoxide production stimulated by zymosan was also inhibited by SP-A at a concentration of 10 micrograms/ml (P < 0.05). Suppression of superoxide production of unstimulated and PMA-stimulated AM was significantly inhibited by anti-SP-A antibody. Superoxide generation by the xanthine and xanthine oxidase system was not affected by the presence of SP-A. Our results suggest that superoxide production of AM can be inhibited by SP-A and that this inhibitory effect on AM is due to a specific effect of SP-A. From these results, it is speculated that SP-A may have a protective role for oxidant injury by AM in the lung.

Pulmonary Surfactant Protein A Inhibits Macrophage Reactive Oxygen Intermediate Production in Response to Stimuli by Reducing NADPH Oxidase Activity

“…We examined the effects of 1-100 g/ml SP-A on superoxide generated by the reaction of xanthine and xanthine oxidase, and found no inhibition of superoxide as detected by CytC reduction. These results are in agreement with those of Katsura et al (13), who found no inhibition of superoxide by 1-10 g/ml rat SP-A in a cell-free system. We also used the EPR spin trap DMPO as a more sensitive probe to study superoxide through the xanthine/ xanthine oxidase reaction, but found no effect by up to 500 g/ml SP-A, which is 25-to 50-fold higher than the concentrations used in our cellular ROI assays.…”

“…SP-A itself has been shown to induce superoxide production in rat alveolar macrophages (11), and to either increase (11,12) or decrease ROI production in response to agonists in rat and canine alveolar macrophages (13,14). Thus, while the data are not easily reconciled, they do suggest a role for SP-A in regulating the macrophage oxidative burst.…”

Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis

“…Specifically, it has been suggested that SP-A-or complement-mediated attachment/phagocytosis by AMs may avoid triggering a cytotoxic response (36,37,62). Our study indicates an SP-A concentration-dependent suppression of RNI production by IFN-γ-primed AMs in response to M. tuberculosis.…”

“…It is also thought that SP-A plays an important role in the modulation of the inflammatory and immunological response (35). Recent studies suggest that SP-A alters oxygen radical production (36,37) and blocks the costimulatory signals crucial for in vitro T-lymphocyte cell activation (38). AMs incubated with SP-A have a decrease in superoxide production, indicating a dampening of the respiratory burst (36,38) and suggesting that SP-A has a protective role against the oxidant injury caused by AMs in the lung.…”

Immunological functions of the pulmonary epithelium

“…Recent data suggest a role for SP-A as an antioxidant in the lower respiratory tract. SP-A, in physiologically relevant concentrations, has been found to inhibit superoxide production by alveolar macrophages stimulated by phorbol 12-myristate-13-acetate (PMA) or zymosan-activated serum [128]. Primarily intracellular antioxidants, e.g.…”