Leptin increases expression of CD11b on human neutrophils
SH Zarkesh-Esfahani, G Pockley, K Norman, RA Metcalfe, C Aylott, P Hellewell, AP Weetman & RJM Ross
Background: Leptin is a multi-functional hormone of which low levels are associated with immuno-deficiency. We and others have shown that leptin promotes secretion of inflammatory cytokines (TNF-alpha and IL-6) by monocytes (1) and activated lymphocytes (2). The leptin receptor (Ob-R) is expressed on neutrophils and leptin enhances oxidative species production by stimulated neutrophils.
Aim: To access whether CD11b expression on human neutrophils is a direct or indirect effect of leptin.
Methods: Human neutrophils either in whole blood or isolated by gradient centrifugation (more than 95 percent pure) were treated with either leptin, TNF-alpha or PMA and expression of CD11b was assessed using flow cytometry.
Results: Leptin (1 micrograms per millilitre) increased the expression of CD11b by neutrophils in whole blood after one hour (Mean plus/minus SEM of mean channel fluorescent of leptin treated; 42.1 plus/minus 3.7 vs PBS treated control; 22 plus/minus 1.3). Leptin (1 micrograms per millilitre) had no effect on expression of CD11b by isolated pure neutrophils despite TNF-alpha showing a profound effect (leptin treated; 36. plus/minus 0.5, PBS control; 38.4 plus/minus 0.4 and TNF-alpha treated; 96.2 plus/minus 0.05).
Conclusion: Leptin stimulates CD11b expression on human neutrophils in whole blood through an indirect effect. We hypothesise that monocytes mediate the effect of leptin on neutrophils, as leptin is known to induce the release of TNF-alpha from monocytes.
References: 1) Lord GM et al (1998) Nature 394: 897-901.
2) Zarkesh-Esfahani SH et al (2001) The journal of immunology 167: 4593-4599.