Pulmonary surfactant transport in alveolar type II cells.

Pulmonary surfactant (PS) is a mixture of several lipids (mainly phosphatidylcholine; PC) and four apoproteins (A, B, C and D). The classical hypothesis of PS transport suggests that PS is synthesized in the endoplasmic reticulum and transported to the lamellar body (LB) via the Golgi apparatus. However, recent studies have raised questions regarding this single route. This study examined, independently, the intracellular trafficking route of three different components of PS, that is, PC, SP-A and SP-B. Alveolar type II cells were isolated from Sprague-Dawley rats or Japanese white rabbits. The cells were cultured with either [3H]choline or [35S]methionine/cysteine with or without brefeldin A, which disassembles the Golgi apparatus. LB was purified from disintegrated cells with sucrose density gradient centrifugation. [3H]PC was extracted from radiolabeled media, cells, and the LB fraction with Bligh-Dyer's method. [35S]SP-A or [35S]SP-B was immunoprecipitated from each sample with a specific antibody. [3H]PC was transported and stored to the LB via a Golgi-independent pathway. [35S]SP-A was transported to the Golgi apparatus, underwent glycosylation, and was then constitutively secreted. The secreted [35S]SP-A was re-uptaken into the LB. [35S]SP-B was transported and stored to the LB via the Golgi-dependent pathway. These results indicate that, rather than a single route, surfactant components take different pathways to reside in the LB. These different pathways may reflect the different nature and role of each surfactant component such as surface tension-lowering activity and innate host defense.

Interleukin-2 abolishes myeloid cell accumulation induced by Lewis lung carcinoma.

Immune aberration in cancer patients can be at least partly ascribed to an accumulation of immature myeloid cells and monocytes/macrophages with immunosuppressive functions. Mice implanted with Lewis lung carcinoma 2 (LL/2) cells show marked splenomegaly as the tumors progress, and this condition is accompanied by impaired T cell activities. We characterized the cells that accumulated in the spleens of LL/2 tumor-bearing mice and attempted to restore the normal cell population by employing interleukin-2 (IL-2). Flow cytometric analysis revealed that the cells expressing Mac1, B7, NK-K1, Gra-1, and MHC class II antigens on their surfaces drastically decreased in number when LL/2 had been engineered to produce IL-2. IL-2 also restored the concanavalin A (ConA)-mediated proliferative response and IL-2 production of the spleen cells. The in vivo growth of IL-2-producing tumors was significantly slower than that of parental LL/2 cells. Therefore, local IL-2 production may reverse systemic immune abnormality by stopping myeloid cell accumulation.