Pulmonary Surfactant Proteins A and D Directly Suppress CD3~+/CD4~+ Cell Function: Evidence for Two Shared Mechanisms

摘要

Pulmonary surfactant is a lipoprotein complex that lowers surface tension at the air-liquid interface of the lung and participates in pulmonary host defense. Surfactant proteins (SP), SP-A and SP-D, modulate a variety of immune cell functions, including the production of cytokines and free radicals. Previous studies showed that SP-A and SP-D inhibit lymphocyte proliferation in the presence of accessory cells. The goal of this study was to deterine whether SP-A and SP-D directly suppress Th cell function. Both proteins inhibited CD3~+/CD4~+ lymphocyte proliferation induced by PMA and ionomycin in an IL-2-independent manner. Both proteins decreased the number of cells entering the S and mitotic phases of the cell cycle. Neither SP-A nor SP-D altered cell viability, apoptosis, or secretion of IL-2, IL-4, or IFN-gamma when Th cells were treated with PMA and ionomycin. However, both proteins attenuated ionomycin-induced cytosolic free calcium ([Ca~(2+)]_i), but not thapsigargin-induced changes in [Ca~(2+]_i. In summary, inhibition of T cell proliferation by SP-A and SP-D occurs via two mechanisms, an IL-2-dependent mechanism observed with accessory cell-dependent T cell mitogans and specific Ag, as well as an IL-2-independent mechanism of suppression that potentially involves attenuation of [Ca~(2+)]_i.