SURFACTANT-ASSOCIATED PROTEIN-A INHIBITS HUMAN LYMPHOCYTE-PROLIFERATION AND IL-2 PRODUCTION

The hyporesponsive state of lung-derived mononuclear leukocytes has be en, in part, attributed to the effects of the lipid rather than the pr otein components of pulmonary surfactant. In the present study, howeve r ever, the results suggest that purified preparations of pulmonary su rfactant-associated protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 mu g/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferatio n of human peripheral blood and tonsillar mononuclear cells in a dose- dependent manner at concentrations as low as 50 pM (6.25 mu g/ml) when added at the initiation of cultures. Addition of SP-A to PHA-stimulat ed peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h aft er PHA was also capable of suppressing [H-3]thymidine incorporation me asured at 72 h. In contrast. concanavalin A (Con A; 2 mu g/ml)-stimula ted PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentration s, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and le ss than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 mu g/ml, respectively. We suggest that the action of SP-A on PHA-stimu lated human PBMC may involve the blocking of a costimulatory signal cr ucial for in vitro T-cell activation.