SECRETION OF CYTOKINES BY RAT ALVEOLAR EPITHELIAL-CELLS - POSSIBLE REGULATORY ROLE FOR SP-A

Cultured alveolar type II cells and pulmonary epithelial (PE) cells in long-term culture were found to secrete colony-stimulating factors (C SF) into the medium in similar fashion to alveolar macrophages. CSF ac tivity was determined by using the in vitro assay for myeloid progenit or cells [colony-forming units in culture (CFU-C)]. Both lipopolisacch aride (LPS) and interleukin-1 alpha (IL-1 alpha) were found to upregul ate the secretion 6.5- to 8-fold from alveolar type II cells and macro phages. However, no stimulatory effect of these factors was observed i n PE cells that release CSF into the medium constitutively, possibly d ue to the conditions of long-term culture. The CSF activity was partia lly neutralized (70% inhibition) by antibodies against murine granuloc yte/macrophage (GM)-CSF and IL-3, thus indicating the presence of both GM-CSF and IL-3-like factors in the CSF. However, the presence of oth er cytokines in the CSF is highly probable. Surfactant-associated prot ein A (SP-A), which is known to play a central role in surfactant home ostasis and function, was also found to upregulate secretion of CSF (a t concentrations of 0.1-5 mu g/ml) from alveolar type II cells and mac rophages. Control cells such as rat peritoneal macrophages, alveolar f ibroblasts, and 3T3/NIH cell line could not be elicited by SP-A to rel ease CSF. The results are discussed in relation to the possible partic ipation of the alveolar epithelial cells in various intercellular sign aling networks. Our studies suggest that alveolar type II cells and SP -A may play an important regulatory role in the modulation of immune a nd inflammatory effector cells within the alveolar space.