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

Abstract

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-1b, tumour necrosis factor a and interferon-g). 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.

Neuronal Expression and Neuritogenic Action of Group X Secreted Phospholipase A2

“…Materials-Rabbit antisera specific for individual human and mouse sPLA 2 s and cDNAs for human sPLA 2 s were described previously (3,9,13). cDNA for the inactive sPLA 2 -X mutant G30S was prepared as described previously (3).…”

“…During the course of our immunohistochemical analyses of various sPLA 2 enzymes in human tissues (9,10,12), we found that sPLA 2 -X is uniquely located in the neuronal fibers in multiple peripheral tissues. On the basis of this observation, we herein examined the expression and potential functions of sPLA 2 -X in neuronal cells.…”

“…However, the regulatory mechanism for this proteolytic processing is still obscure, because the active enzyme is spontaneously secreted from sPLA 2 -X-transfected cells during culture (3,4). Recent immunohistochemical analyses have demonstrated the expression of sPLA 2 -X in macrophages and alveolar epithelial cells in the lung (8,9), spermatogenic cells and duct epithelium in male reproductive organs (10), and in atherosclerotic plaques (11). Although these distributions suggest the potential roles of sPLA 2 -X in airway inflammation, reproduction, and atherosclerosis, the true physiological and pathological functions of this particular sPLA 2 enzyme are still a subject of debate.…”

Group V Phospholipase A2 in Bone Marrow-derived Myeloid Cells and Bronchial Epithelial Cells Promotes Bacterial Clearance after Escherichia coli Pneumonia

“…The observations that GV sPLA 2 can hydrolyze Gram-negative bacterial phospholipids (6) and that phagocytosis by peritoneal macrophages is modulated by GV sPLA 2 (7) suggests that GV sPLA 2 participates in the killing of bacteria by leukocytes (5). GV sPLA 2 can be expressed by macrophages (7,8), mast cells (9,10), airway smooth muscle cells (11), and bronchial epithelial cells (12) in mice and by alveolar macrophages, bronchial epithelial cells, and interstitial fibroblasts in patients with pneumonia, where expression of GV sPLA 2 correlates with the severity of inflammation (13). Overexpression of GV sPLA 2 leads to increased PGE 2 biosynthesis by cultured bronchial epithelial cells (13) and to surfactant degradation, respiratory distress, and neonatal lethality in transgenic mice that constitutively express the enzyme under an actin promotor (14).…”

“…GV sPLA 2 can be expressed by macrophages (7,8), mast cells (9,10), airway smooth muscle cells (11), and bronchial epithelial cells (12) in mice and by alveolar macrophages, bronchial epithelial cells, and interstitial fibroblasts in patients with pneumonia, where expression of GV sPLA 2 correlates with the severity of inflammation (13). Overexpression of GV sPLA 2 leads to increased PGE 2 biosynthesis by cultured bronchial epithelial cells (13) and to surfactant degradation, respiratory distress, and neonatal lethality in transgenic mice that constitutively express the enzyme under an actin promotor (14). Together, these observations suggest a central role for GV sPLA 2 in the innate immune response to bacterial pneumonia.…”