ABSTRACT
In contrast to leukocytosis, paraneoplastic hypereosinophilia is uncommon in lung cancer. We present a patient with large-cell carcinoma of the lung, in which cancer cells generate large amounts of GM-CSF leading to a leukemoid reaction with prominent hypereosinophilia and potentially involved in autocrine tumor stimulation.
Subject(s)
Carcinoma, Large Cell/complications , Carcinoma, Large Cell/metabolism , Eosinophilia/etiology , Granulocyte Colony-Stimulating Factor/blood , Lung Neoplasms/complications , Lung Neoplasms/metabolism , Carcinoma, Large Cell/drug therapy , Eosinophilia/diagnosis , Fatal Outcome , Humans , Lung Neoplasms/drug therapy , Male , Middle AgedABSTRACT
BACKGROUND: The mast cell's (MC) ability to rapidly release presynthesized mediators allows it to play a critical role in the immune system's first-line response to pathogens. Although recent research has illuminated the role of MCs in bacterial infection, little is known about how non-pathogenic bacteria influence MC responses. OBJECTIVE: To characterize the influence of non-pathogenic Escherichia coli bacteria on MCs. RESULTS: High concentrations of live E. coli strongly down-modulated the degranulation of murine peritoneal MCs under all activator conditions. Bacteria did not induce MC degranulation by themselves, and staining of MCs showed they were still entirely viable. Dead bacteria and bacterial supernatant had no effect on MC degranulation. Ex vivo experiments confirmed that E. coli exposure down-modulates subsequently induced MC degranulation and that this effect lasts for up to a few days after exposure. CONCLUSION: Our results show that high doses of non-pathogenic E. coli bacteria can function as a strong, direct inhibitor of MC degranulation. This suggests a possible basis for future antiallergic treatment or prophylaxis with commensal bacteria, i.e. probiotics.
Subject(s)
Cell Degranulation/physiology , Escherichia coli , Mast Cells/physiology , Animals , Apoptosis , Calcimycin/pharmacology , Cell Degranulation/drug effects , Cell Line , Cell Survival , Dactinomycin/pharmacology , Dinitrophenols/pharmacology , Escherichia coli/pathogenicity , Flow Cytometry , Immunoglobulin E/pharmacology , Mast Cells/drug effects , Mice , Mice, Inbred C57BL , Peritoneum/cytology , Serotonin/analysis , Serotonin/metabolism , Serum Albumin/pharmacology , Tritium/analysisABSTRACT
Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assessed skin responses to ET-1 injections, we observed prominent mast cell degranulation and mast cell-dependent inflammation. Since mast cells also critically contributed to UV-induced inflammation, we determined the ET-1-dependent inflammatory response to UV in the absence and presence of these cells. Interestingly, ETA blockade did not decrease UV-induced inflammation in mast cell-deficient mice, unless these mice had been adoptively transferred with mast cells before irradiation. This indicates that skin inflammation due to UV irradiation is caused in part by ET-1 acting on skin mast cells.
Subject(s)
Cell Degranulation/radiation effects , Dermatitis/metabolism , Endothelin-1/metabolism , Mast Cells/metabolism , Receptor, Endothelin A/metabolism , Ultraviolet Rays/adverse effects , Animals , Cell Degranulation/genetics , Dermatitis/pathology , Dose-Response Relationship, Radiation , Endothelin A Receptor Antagonists , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Mast Cells/pathology , Mice , Mice, TransgenicABSTRACT
Snake or honeybee envenomation can cause substantial morbidity and mortality, and it has been proposed that the activation of mast cells by snake or insect venoms can contribute to these effects. We show, in contrast, that mast cells can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which can degrade venom components. Mast cells also significantly reduced the morbidity and mortality induced by honeybee venom. These findings identify a new biological function for mast cells in enhancing resistance to the morbidity and mortality induced by animal venoms.
