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 sPLA₂ (secretory phospholipase A₂) enzymes have been identified in mammals, the localization and functions of individual enzymes in human pathologic tissues still remain obscure. In the present study, we have examined the expression and function of sPLA₂s in human lung-derived cells and in human lungs with pneumonia. Group IID, V and X sPLA₂s were expressed in cultured human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts with distinct requirement for cytokines (interleukin-1β, tumour necrosis factor α and interferon-γ). Lentivirus- or adenovirus-mediated transfection of various sPLA₂s into BEAS-2B or normal human pulmonary fibroblast cells revealed that group V and X sPLA₂s increased arachidonate release and prostaglandin production in both cell types, whereas group IIA and IID sPLA₂s failed to do so. Immunohistochemistry of human lungs with pneumonia demonstrated that group V and X sPLA₂s were widely expressed in the airway epithelium, interstitium and alveolar macrophages, in which group IID sPLA₂ was also positive, whereas group IIA sPLA₂ was restricted to the pulmonary arterial smooth muscle layers and bronchial chondrocytes, and group IIE and IIF sPLA₂s were minimally detected. These results suggest that group V and X sPLA₂s affect lung pathogenesis by facilitating arachidonate metabolism or possibly through other functions.