INHIBITORY EFFECT OF PULMONARY SURFACTANT PROTEIN-A AND PROTEIN-D ON ALLERGEN-INDUCED LYMPHOCYTE-PROLIFERATION AND HISTAMINE-RELEASE IN CHILDREN WITH ASTHMA

The role of pulmonary surfactant proteins in the pathogenesis of airwa y inflammation and the impact on asthma has not been elucidated. This study was designed to examine the effect of surfactant proteins A (SP- A) and D (SP-D) on phytohemagglutinin- (PHA) and mite allergen Dermato phogoides pferonyssinus (Der p)-induced histamine release and the prol iferation of peripheral blood mononuclear cells (PBMC) in children wit h asthma in stable condition (n = 21), asthmatic children during acute attacks (n = 9), and age-matched control subjects (n = 7). The result s show that SP-A and SP-D were able to reduce the incorporation of [H- 3]thymidine into PBMC in a dose-dependent manner. In addition to the i ntact, native SP-A and SP-D proteins, a recombinant peptide composed o f the neck and carbohydrate recognition domain (CRD) of SP-D [SP-D(N/C RD)] was also found to have the same suppressive effect on lymphocyte proliferation. This effect was abolished by the presence of 100 mM man nose (for SP-A) or maltose (for SP-D) in the culture medium, which sug gested that the CRD regions of SP-A and SP-D may interact with the car bohydrate structures on the surface molecules of lymphocytes. The inhi bitory effects of surfactant proteins on PHA- and Der p-stimulated lym phocyte responses were observed in stable asthmatic children and age-m atched control subjects, while only a mild suppression (< 25%) was see n in activated lymphocytes derived from asthmatic children with acute attacks. SP-A and SP-D were also found to inhibit allergen-induced his tamine release, in a dose-dependent manner, in the diluted whole blood of asthmatic children. We conclude that both SP-A and SP-D can inhibi t histamine release in the early phase of allergen provocation and sup press lymphocyte proliferation in the late phase of bronchial inflamma tion, the two essential steps in the development of asthmatic symptoms . It appears that SP-A and SP-D may be protective against the pathogen esis of asthma.