Leukotriene B4 receptor levels and intracellular calcium signalling in polymorphonuclear leukocytes from patients with Crohn's disease
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OBJECTIVE: To investigate the leukotriene B4 (LTB4) signal transducing mechanism in polymorphonuclear neutrophils (PMNs) from patients with Crohn's disease.
METHODS: Cytosolic free calcium ([Ca2+]i), inositol (1,4,5)-trisphosphate [(1,4,5)-IP3] chemotaxis, LTB4 receptor number and affinity were investigated in peripheral PMNs from 11 patients with Crohn's disease and 11 healthy controls.
RESULTS: There was a slight reduction (P = 0.31) in the number of LTB4 receptor sites per cell expressed on PMNs (mean Bmax 931) from nine of the 11 patients studied compared with the healthy controls (mean Bmax 1095). LTB4-mediated (1,4,5)-IP3 formation and the increase in [Ca2+]i were markedly decreased in PMNs from the 11 patients with Crohn's disease [(1,4,5)-IP3, mean +/- SEM 12 +/- 0.84 and 27.4 +/- 1.4 pmol/l/tube for patients and controls, respectively; [Ca2+]i, mean +/- SEM 295 +/- 2.75 and 598 +/- 4.7 nmol/l for patients and controls, respectively]. The decrease in calcium might be related to the decrease in Bmax (P < 0.05). Ionomycin, a calcium ionophore which bypasses the initial steps of LTB4 receptor activation, showed only a minor difference in peak [Ca2+]i between PMNs from patients and controls. LTB4-directed chemotaxis showed that the sensitivity to suboptimal concentrations of LTB4 (1.0 nmol/l) was significantly depressed in PMNs from patients (P < 0.05).
CONCLUSION: Peripheral PMNs from patients with Crohn's disease had a small deficit in the expression of LTB4 receptors. This deficiency was paralleled by marked alterations in cellular signalling. Whether these results are specific to Crohn's disease or simply result from the exposure of circulating PMNs to elevated levels of LTB4 remains to be established.
|Journal||European journal of gastroenterology & hepatology|
|Number of pages||8|
|Publication status||Published - Apr 1995|
- Adult, Calcium/analysis, Chemotaxis, Crohn Disease/physiopathology, Cytosol/chemistry, Female, Humans, Inositol 1,4,5-Trisphosphate/metabolism, Leukotriene B4/physiology, Male, Middle Aged, Neutrophils/chemistry, Receptors, Leukotriene B4/analysis, Signal Transduction