Bronchoalveolar lavage fluid endotoxin elevation in human single lung transplant recipients during rejection.

Endotoxin has been implicated as an aetiological factor in liver transplant rejection and acute graft-versus-host disease. To investigate the role of endotoxin in human single lung transplant rejection we measured the level of endotoxin in bronchoalveolar lavage (BAL) fluid from six subjects at baseline and during rejection, which was defined histologically from transbronchial biopsy. Differential cell counts of BAL fluid cells, the levels of protein and albumin in BAL fluid, and serum albumin levels were also examined. BAL fluid albumin to serum ratio was calculated to evaluate alveolar-capillary leakage. A significant elevation of BAL fluid endotoxin with rejection compared with baseline was observed. Standardizing endotoxin levels to BAL fluid volume, protein, or albumin were all of similar significance. Examination of BAL fluid cell population revealed a significant elevation in the percentage of lymphocytes with rejection. No significant difference between BAL fluid protein levels, BAL fluid albumin levels. BAL fluid albumin to protein ratio, serum albumin levels, or BAL fluid albumin to serum albumin ratio was seen with rejection. We conclude that BAL fluid endotoxin levels increase during lung rejection, endotoxin levels can be accurately standardized to millilitres of BAL fluid, and abnormal alveolar-capillary leakage does not appear to account for the increased BAL fluid endotoxin.

Cyclic AMP stimulates platelet-derived growth factor B chain mRNA expression in murine macrophage cell lines.

Prostaglandin E(2) plays a role in cytokine production presumably by altering intracellular levels of cAMP. In this paper, we report on the differential expression of cytokine genes in murine macrophages in response to stimulation with activators of cAMP. Macrophages were cultured with or without cAMP activators in the presence or absence of LPS. Prior to treatment, macrophages do not express interleukin-1beta, but do express low levels of tumour necrosis factor alpha and platelet-derived growth factor B chain mRNAs. After culture with cAMP-inducers, including PGE(2), dibutyryl cAMP and forskolin, PDGF B chain mRNA is induced. Forskolin, for example, induced expression PDGF B chain mRNA to a level ranging from 25% to 200% of the level induced by LPS in 6 h. In contrast, cAMP-inducers enhance the expression of IL-1beta and TNF-alpha mRNAs, but only in the presence of LPS. The combination of forskolin and LPS does not appear to act synergistically on PDGF B chain mRNA levels, suggesting that LPS-stimulated effects are not mediated through a cAMP-dependent pathway. Furthermore, macrophages differentially express cytokine genes in response to treatment with inducers of intracellular cAMP.