Dynorphin expression, processing and receptors in the alveolar macrophages, cancer cells and bronchial epithelium of lung cancer patients.
Functional evidence suggests that opioid peptides such as dynorphin are involved in the regulation of airway macrophage functions and of human cancer growth. However, anatomical evidence for components of a putative dynorphin network within lung cancer patients is scarce. Tissue from lung cancer patients was examined immunohistochemically for all components of a local dynorphin (DYN) network. Double immunofluorescence microscopy analysis revealed colocalization of the opioid precursor PDYN with its end-product DYN, and key processing enzymes prohormone convertases 1 and 2 and carboxypeptidase E, as well as the kappa-opioid receptor (KOR) within alveolar macrophages and cancerous cells in varying degrees among patients. Moreover, chromograninA-immunoreactive pulmonary neuroendocrine cells expressing DYN were close to substance P- and KOR-immunoreactive sensory nerves. Our findings give a first hint of a neuroanatomical basis for a peripheral DYN network, conceivably regulating pulmonary, immune and cell-proliferative functions within the human lung, most likely in a paracrine/autocrine fashion.
Mousa
Shaaban A
SA
Department of Anesthesiology and Intensive Care Medicine, Charité-Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charite Mitte, Berlin, Germany.
Krajnik
Malgorzata
M
Sobanski
Piotr
P
Kowalewski
Janusz
J
Bloch-Boguslawska
Elzbieta
E
Zylicz
Zbigniew
Z
Schäfer
Michael
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D043423:Carboxypeptidase H / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004399:Dynorphins / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000378:metabolism*; D045664:Proprotein Convertase 1 / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004745:Enkephalins; D018377:Neurotransmitter Agents; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D004399:Dynorphins; C033660:preproenkephalin; D043423:Carboxypeptidase H; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2