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- Dadfar, E, et al.
(författare)
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Granulocyte extravasation and recruitment to sites of interstitial inflammation in patients with renal failure
- 2004
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Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 24:3, s. 330-339
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> We have shown that leukocytes collected from sites of interstitial inflammation in patients on hemodialysis have a disturbed expression of CD11b compared to cells from healthy subjects. The aim of the present study was to study adhesion molecule expression on granulocytes in the peripheral circulation and at sites of interstitial inflammation in patients with renal failure. <i>Methods:</i> Two skin blisters were raised in 10 patients and 19 healthy subjects and interstitial exudates collected (0 h). Skin chambers were applied and exposed to buffer or serum for 10 h in order to induce an intermediate and an intense interstitial inflammation. Cells and blister fluid were collected for determination of leukocyte count, CD11b/CD62L expression, interleukin-8 (IL-8) concentration in the interstitium and blister activity in terms of CD11b up-regulation. <i>Results:</i> At the sites of intermediate and intense inflammation, granulocytes from patients with renal failure showed significantly higher expression of CD62L (p < 0.01 and p < 0.001, respectively) and significantly lower expression of CD11b (p < 0.0001 and p < 0.0001, respectively) compared to corresponding cells from healthy subjects. The interstitial concentration of IL-8 was significantly lower at the sites of intermediate (p < 0.005) and intense inflammation (p < 0.05) in patients with renal failure compared to in healthy subjects. In order to explore whether the decreased CD11b expression observed in patients is due to the interstitial milieu, blister exudates from patients and healthy subjects were incubated with leukocytes from healthy blood donors. Blister exudates from patients had a similar capacity to mobilize CD11b on granulocytes in vitro compared with blister exudates from healthy subjects. There was no consistent correlation between the expression of adhesion molecules on granulocytes in the interstitium and the concentration of IL-8 or the total interstitial concentration of chemotactic mediators. <i>Conclusion:</i> Constitutive cellular determinants are probably involved in the disturbed expression of adhesion molecules on granulocytes at sites of interstitial inflammation in patients with renal failure.
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- Dadfar, E, et al.
(författare)
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Newly recruited human monocytes have a preserved responsiveness towards bacterial peptides in terms of CD11b up-regulation and intracellular hydrogen peroxide production
- 2007
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 148:3, s. 573-582
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Tidskriftsartikel (refereegranskat)abstract
- The transmigration of peripheral human monocytes to the interstitium is a fundamental step in the host-defence mechanism against infections. Little is known about the state of function of in vivo transmigrated interstitial monocytes prior to differentiation into macrophages and dendritic cells. We hypothesized that newly recruited interstitial monocytes have a preserved responsiveness against bacterial-related peptides, giving them a specific role in the immediate defence against invading pathogens. In order to test this hypothesis, we explored the responsiveness of in vivo transmigrated as well as peripheral monocytes, in terms of CD11b expression and H2O2 production towards the bacterial-related peptide formylmethionylleucylphenylalanine (fMLP) by the use of a skin chamber technique. In addition, we analysed the concentration of interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor (TNF)-α in the skin blister exudates and in the circulation. We demonstrate that in vivo-transmigrated monocytes had a fivefold higher CD11b expression compared to monocytes obtained from the peripheral circulation. fMLP exposure induced a significantly higher CD11b expression on transmigrated cells compared to peripheral monocytes. In addition, newly recruited monocytes had a preserved H2O2 production. The interstitial concentration of IL-8, MCP-1 and TNF-α was significantly higher in blister exudates compared to that in the peripheral circulation. Thus, in vivo transmigrated human monocytes preserve their capacity to respond towards bacterial peptides in terms of CD11b up-regulation and H2O2 generation. These data strengthen a role for newly recruited interstitial human monocytes in the immediate defence against invading pathogens.
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