TY - JOUR
T1 - Group V phospholipase A 2 in bone marrow-derived myeloid cells and bronchial epithelial cells promotes bacterial clearance after Escherichia coli pneumonia
AU - Degousee, Norbert
AU - Kelvin, David J.
AU - Geisslinger, Gerd
AU - Hwang, David M.
AU - Stefanski, Eva
AU - Wang, Xing Hua
AU - Danesh, Ali
AU - Angioni, Carlo
AU - Schmidt, Helmut
AU - Lindsay, Thomas F.
AU - Gelb, Michael H.
AU - Bollinger, James
AU - Payre, Christine
AU - Lambeau, Gérard
AU - Arm, Jonathan P.
AU - Keating, Armand
AU - Rubin, Barry B.
PY - 2011/10/14
Y1 - 2011/10/14
N2 - Group V-secreted phospholipase A 2 (GV sPLA 2) hydrolyzes bacterial phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role of GV sPLA 2 in the pathophysiology of Escherichia coli pneumonia. Inflammatory cells and bronchial epithelial cells both express GV sPLA 2 after pulmonary E. coli infection. GV -/- mice accumulate fewer polymorphonuclear leukocytes in alveoli, have higher levels of E. coli in bronchoalveolar lavage fluid and lung, and develop respiratory acidosis, more severe hypothermia, and higher IL-6, IL-10, and TNF-α levels than GV +/+ mice after pulmonary E. coli infection. Eicosanoid levels in bronchoalveolar lavage are similar in GV +/+ and GV -/- mice after lung E. coli infection. In contrast, GV +/+ mice have higher levels of prostaglandin D 2 (PGD 2), PGF 2α, and 15-keto-PGE 2 in lung and express higher levels of ICAM-1 and PECAM-1 on pulmonary endothelial cells than GV -/- mice after lung infection with E. coli. Selective deletion of GV sPLA 2 in non-myeloid cells impairs leukocyte accumulation after pulmonary E. coli infection, and lack of GV sPLA 2 in either bone marrow-derived myeloid cells or non-myeloid cells attenuates E. coli clearance from the alveolar space and the lung parenchyma. These observations show that GV sPLA 2 in bone marrow-derived myeloid cells as well as non-myeloid cells, which are likely bronchial epithelial cells, participate in the regulation of the innate immune response to pulmonary infection with E. coli.
AB - Group V-secreted phospholipase A 2 (GV sPLA 2) hydrolyzes bacterial phospholipids and initiates eicosanoid biosynthesis. Here, we elucidate the role of GV sPLA 2 in the pathophysiology of Escherichia coli pneumonia. Inflammatory cells and bronchial epithelial cells both express GV sPLA 2 after pulmonary E. coli infection. GV -/- mice accumulate fewer polymorphonuclear leukocytes in alveoli, have higher levels of E. coli in bronchoalveolar lavage fluid and lung, and develop respiratory acidosis, more severe hypothermia, and higher IL-6, IL-10, and TNF-α levels than GV +/+ mice after pulmonary E. coli infection. Eicosanoid levels in bronchoalveolar lavage are similar in GV +/+ and GV -/- mice after lung E. coli infection. In contrast, GV +/+ mice have higher levels of prostaglandin D 2 (PGD 2), PGF 2α, and 15-keto-PGE 2 in lung and express higher levels of ICAM-1 and PECAM-1 on pulmonary endothelial cells than GV -/- mice after lung infection with E. coli. Selective deletion of GV sPLA 2 in non-myeloid cells impairs leukocyte accumulation after pulmonary E. coli infection, and lack of GV sPLA 2 in either bone marrow-derived myeloid cells or non-myeloid cells attenuates E. coli clearance from the alveolar space and the lung parenchyma. These observations show that GV sPLA 2 in bone marrow-derived myeloid cells as well as non-myeloid cells, which are likely bronchial epithelial cells, participate in the regulation of the innate immune response to pulmonary infection with E. coli.
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U2 - 10.1074/jbc.M111.262733
DO - 10.1074/jbc.M111.262733
M3 - Article
C2 - 21849511
AN - SCOPUS:80053930398
SN - 0021-9258
VL - 286
SP - 35650
EP - 35662
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -