Regeneration Processes in the Kidney after Acute Injury: Role of Infiltrating Cells

Abstract

The transient presence of infiltrated leukocytes in the kidney during acute renal failure as well as the location of these cells within the renal interstitium suggest their association with tubular injury and/or regeneration. To date, however, neither a positive nor a negative contribution of these cells to the pathophysiology of this disease could be unambiguously demonstrated. Ill-defined methods for identifying interstitial leukocytes have added to the controversy concerning the role of inflammatory cells in renal regeneration. The current literature survey presents a qualitative description of the renal interstitial accumulation of leukocytes as observed in some acute renal failure models, with special attention to those displaying acute tubular necrosis of particular nephron subsegments. We conclude that lethal or sublethal injury to renal tubular epithelial cells following toxic or ischemic insults leads to the manifestation of an interstitial mononuclear cell infiltrate. Whereas macrophages and T lymphocytes almost invariably take part, the former being the dominant cell population with respect to both magnitude and presence over time, polymorphonuclear cells seem to be significantly increased only in the case of pyelonephritis. Infiltrating cells have often been regarded rather harmful to the tissue, mainly due to the quite well understood injuring capacity of the latter. On the other hand, we speculate mononuclear leukocytes through their potential of producing different cytokines and growth factors (FGF, TGF-α, EGF-like, IL-2, etc.) might well play an initiating and mediating role in renal regeneration after acute tubular necrosis. Therefore, the role of infiltrating leukocytes in the injury/regeneration process during acute renal failure remains highly controversial and should be further elucidated.

Possible Involvement of Myofibroblasts in Cellular Recovery of Uranyl Acetate-Induced Acute Renal Failure in Rats

“…In fact, several studies have reported the presence of infiltrating cells in the interstitium after acute renal injury. 24 In our model, ED 1-positive monocytes/ macrophages did infiltrate transiently in the interstitium. Specific association of them with initially necrotic tubules surrounded by myofibroblasts, however, was not evident.…”

“…At present, fibroblast growth factors-1 and -7 and hepatocyte growth factor may be possible candidates for cytokines secreted by myofibroblasts in renal interstitium. [32][33][34][35] Transient interstitial infiltrating cells 24,32,36 as well as tubular cells 21,22,[37][38][39] are also a possible source of cytokines, which can promote regeneration of the damaged tubules. Indeed, in the present study transient infiltration of interstitial monocytes/macrophages could be found in some association with regenerating tubules.…”

IFN-Inducible Protein 10 (CXCL10) Regulates Tubular Cell Proliferation in Renal Ischemia-Reperfusion Injury

“…Tubular epithelial cells may produce growth factors (FGF, TGF-α, EGF-like, IL-2, osteopontin, etc.) at regenerative wound margins associated with leukocyte infiltration [30,31,32]. It is likely that the inflammatory infiltrating leukocytes secret cytokines and chemokines that may regulate growth factor production by resident renal cells.…”

Molecular mechanisms of enhanced renal cell division in protection againstS-1,2-dichlorovinyl-l-cysteine-induced acute renal failure and death

“…Some of the candidate mediators of preconditioning are heat shock protein molecular chaperones (9), activation of the nitric oxide synthase pathways (42), stimulation of PPAR receptors (47), induction of endoplasmic reticulum and stress proteins (24), activation of ERK 1/2 (43), and activation of a phosphatidylinosital 3-kinase Akt/PKB pathway (2). When a toxicant causes acute renal tubular necrosis, the remaining viable quiescent tubular epithelial cells are triggered to enter the cell cycle, which eventually (20). Several investigators examined the production and localization of growth factors and their ability to stimulate cell growth and proliferation in regenerating proximal tubules after chemical or ischemia/reperfusion injury (4,7,25,35,40,50).…”