Immune regulation of human colonic electrolyte transport in vitro.
The role of lamina propria cells in regulating human colonic ion transport was investigated in vitro. Normal human colonic mucosae were mounted in Ussing chambers, and short circuit current changes (delta SCC) were monitored in response to immune cell activation. Anti-human immunoglobulin E (anti-IgE) and formyl-Methionyl-Leucyl-Phenylalanine (fMLP) were used to stimulate mast cells and phagocytes respectively. Anti-IgE (100 micrograms/ml) and fMLP (100 microM) evoked rapid onset, inward delta SCC (mean (SEM) max delta SCC 19.3 (2.8) and 29.4 (4.7) microA/0.63 cm2 respectively). A pharmacological approach was used to identify the charge carrying ion species and to characterise mediators involved in the SCC response. Responses to each secretagogue were significantly attenuated by bumetanide, indicating that the delta SCC was at least partly due to electrogenic chloride secretion. Piroxicam reduced the delta SCC to mast cell and phagocyte activation by 91.1 (3.4)% and 48.2 (25.2)% respectively, implicating eicosanoids as mediators of the responses. Mepyramine (100 microM) reduced the SCC responses to anti-IgE by 79.6 (12.0)% but did not significantly alter delta SCC responses to fMLP. Desensitisation to repeated anti-IgE or fMLP stimulation, and cross desensitisation between each of the stimuli, were features of immune cell activation. In summary, we have shown that activation of immune cells can stimulate electrogenic chloride secretion. Such events in vivo will result in gradient driven secretory diarrhoea, which may occur as a protective response to enteric-dwelling parasites, or as a feature of local bowel inflammation.
Stack
W A
WA
Department of Pharmacology, University College Dublin, Ireland.
Keely
S J
SJ
O'Donoghue
D P
DP
Baird
A W
AW
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003967:Diarrhea / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013268:Stimulation, Chemical
D000888:Antibodies, Anti-Idiotypic; D002712:Chlorides; D002034:Bumetanide; D010894:Piroxicam; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011738:Pyrilamine