Effect of pentoxifylline on the inhibition of surfactant synthesis induced by TNF-alpha in human type II pneumocytes.
Tumor necrosis factor alpha (TNF-alpha) seems to play an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This study was designed to determine the effect of TNF-alpha and pentoxifylline (PTXF) on surfactant synthesis by isolated human type II pneumocytes. In order to isolate the pneumocytes, lungs obtained from both previously healthy multiple organ donors (n = 11) and patients who underwent surgical excision for lung cancer (n = 8) were used. Surfactant synthesis was measured by the incorporation of labeled glucose into the two most important phospholipid components of surfactant: phosphatidylcholine (PC) and phosphatidylglycerol (PGL). The pneumocytes of the donor group showed a greater degree of PC synthesis than those from the cancer group (3.44 +/- 0.19 versus 2.15 +/- 01.5 pmol/micrograms protein, p < 0.001). The synthesis of PC by pneumocytes in both the donor (1.13 +/- 0.19 versus 3.44 +/- 0.19 pmol/micrograms protein, p < 0.01) and cancer (0.99 +/- 0.11 versus 2.15 +/- 0.15 pmol/micrograms protein, p < 0.01) groups was decreased by TNF-alpha (100 ng/ml). This effect was blocked by PTXF (100 micrograms/ml), a substance that also increased PC production in the control-group pneumocytes from cancer patients, the final PC levels being similar to those of the donors in the absence of TNF-alpha. These results suggest that one of the mechanisms of TNF-alpha participation in the pathophysiology of ARDS is inhibition of surfactant synthesis, and support the hypothesis of in vivo production of TNF-alpha in lung-cancer patients, with subsequent chronic exposure of the lung epithelial cells to this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
Balibrea-Cantero
J L
JL
Department of Surgery (Hospital Universitario San Carlos), Universidad Complutense of Madrid, Spain.
Arias-Diaz
J
J
Garcia
C
C
Torres-Melero
J
J
Simon
C
C
Rodriguez
J M
JM
Vara
E
E
D000328:Adult; D000704:Analysis of Variance; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000032:analysis / Q000096:biosynthesis; D010715:Phosphatidylglycerols / Q000032:analysis / Q000096:biosynthesis; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000737:chemistry / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline