Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic function in human lung-derived cells

Although a number of sPLA(2) (secretory phospholipase A(2)) enzymes have been identified in mammals, the localization and functions of individual enzymes in human parthologic tissues still remain obscure. In the present study, we have examined the expression and function of sPLA(2)s in human lung-derived cells and in human lungs with pneumonia. Group IID, V and X sPLA(2)s were expressed in cultured human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts with distinct requirement for cytokines (interleukin-1 beta, tumour necrosis factor a and interferon-gamma). Lentivirus- or adenovirus-mediated transfection of various sPLA(2)s into BEAS-2B or normal human pulmonary fibroblast cells revealed that group V and X sPLA(2)s increased arachidonate release and prostaglandin production in both cell types, whereas group IIA and IID sPLA(2)s failed to do so. Immunohistochemistry of human lungs with pneumonia demonstrated that group V and X sPLA(2)S were widely expressed in the airway epithelium, interstitium and alveolar macrophages, in which group IID sPLA, was also positive, whereas group IIA sPLA, was restricted to the pulmonary arterial smooth muscle layers and bronchial chondrocytes, and group IIE and IIF sPLA(2)s were minimally detected. These results suggest that group V and X sPLA(2)s affect lung pathogenesis by facilitating arachidonate metabolism or possibly through other functions.