Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury

Abstract

During renal ischemia-reperfusion, local and distant tissue injury is caused by an influx of neutrophils into the affected tissues. Here we measured the kinetics of margination and transmigration of neutrophils in vivo in the kidney and lungs following renal ischemia-reperfusion. After bilateral renal injury, kidney neutrophil content increased threefold at 24 h. The neutrophils were found primarily in the interstitium and to a lesser degree marginated to the vascular endothelium. These interstitial neutrophils had significantly lower levels of intracellular IFN-γ, IL-4, IL-6, and IL-10 a tendency for decreased amounts of IL-4 and TNF-α compared to the marginated neutrophils. Localization of the neutrophils to the kidney interstitium was confirmed by high resolution microscopy and these sites of transmigration were directly associated with areas of increased vascular permeability. Activation of the adenosine 2A receptor significantly decreased both kidney neutrophil transmigration by about half and vascular permeability by about a third. After unilateral renal ischemia-reperfusion, the unclipped kidney and lungs did not accumulate interstitial neutrophils or have increased vascular permeability despite a marked increase of neutrophil margination in the lungs. Our findings suggest there is a sequential recruitment and transmigration of neutrophils from the vasculature into the kidney interstitium at the site of tissue injury following renal ischemia-reperfusion.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men

“…NGAL from circulating activated neutrophils are primarily reflected in plasma or serum but it can not be ruled out that NGAL from activated neutrophils also contributes to u-NGAL concentrations. During AKI both infiltration of neutrophils in the kidney [38] or glomerular filtration of circulating NGAL may contribute to urinary concentrations of NGAL [39]. The origin of u-NGAL in this setting of elderly but relatively healthy humans is not fully known, however we speculate that a major part of the measured u-NGAL derives from tubular endothelial cells rather than from circulating neutrophils.…”

Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury

“…Recruitment of leukocytes, particularly neutrophils and macrophages, is a hallmark of IRI [40][41][42] and both cell types are actively involved in tissue damage in ischemiarelated ARF. 41,43 The impaired leukocyte influx seen in kidneys from both CD47 2/2 mice (and WT mice treated with a CD47 blocking antibody) may be in part as a consequence of reduced proinflammatory cytokine and chemokine levels (particularly CXCL2), and may account for the lower degree of renal dysfunction and tissue damage compared with WT controls.…”

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

“…4 Our group and others have demonstrated the role of different immune cell populations in kidney IRI. [5][6][7][8][9] Recently, an intimate connection between the intestine and the kidneys has been proposed. 10,11 Established data have already shown that modification of microbiota composition could affect the outcome of glomerulopathies, and recent data indicate that renal inflammation is associated with the production of uremic toxins by the intestine and with augments intestinal permeability, leading to the onset of systemic inflammation.…”