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Endothelin-1 increases intracellular calcium in human monocytes and causes production of interleukin-6
M A McMillen1, M Huribal, M E Cunningham
1Department of Surgery, Bridgeport Hospital, Yale University, West Haven, CT.
Insights
Endothelin-1, a peptide from injured endothelium, boosts monocyte intracellular calcium and interleukin-6 (IL-6) production. This peptide did not affect interleukin-1 (IL-1) levels in human monocytes.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Endothelin-1 is a peptide released by injured or ischemic endothelium.
- Monocytes play a crucial role in inflammatory and immune responses.
Purpose of the Study:
- To investigate the effect of endothelin-1 on human monocyte intracellular calcium.
- To determine if endothelin-1 influences the production of interleukin-1 (IL-1) and interleukin-6 (IL-6) by monocytes.
Main Methods:
- A prospective controlled laboratory study was conducted using human monocytes from healthy donors.
- Intracellular calcium levels were measured using fluorometry.
- Monocytes were stimulated with purified endotoxin or endothelin for 24 hours in tissue culture.
Main Results:
- Endothelin-1 significantly increased intracellular calcium concentration in human monocytes.
- Endothelin-1 stimulated the production of IL-6 by monocytes, with levels comparable to lipopolysaccharide controls.
- Endothelin-1 did not affect IL-1 production or intracellular calcium in neutrophils and lymphocytes.
Conclusions:
- Endothelin-1 elevates intracellular calcium in monocytes.
- Endothelin-1 induces IL-6 production in monocytes, suggesting a role in inflammatory processes.
Objective:
To define whether endothelin-1, a peptide produced by injured/ischemic endothelium, has any effect on monocyte intracellular calcium and the production of interleukin (IL)-1 and IL-6.
Design:
Prospective controlled laboratory study. Human monocytes from healthy donors were assayed for intracellular calcium by fluorometry and were stimulated for 24 hrs in tissue culture with purified endotoxin or endothelin.
Setting:
Veterans Affairs Medical Center surgical critical care basic science laboratory.
Measurements And Main Results:
Endothelin-1 increased the intracellular calcium concentration in fura-2 loaded human monocytes to a mean value of 37 +/- 4 nmol. Phytohemagglutinin increased intracellular calcium in control monocytes to a mean value of 97 +/- 12 nmol (n = 15; p < .001). Endothelin had no effect on neutrophil or lymphocyte intracellular calcium. Monocytes incubated with 10(-9) M endothelin significantly increased IL-6 production to values nearly as high as the lipopolysaccharide controls, but did not increase IL-1 production (n = 8; p < .01).
Conclusion:
Endothelin-1 increased intracellular calcium in monocytes and caused production of IL-6.