Postischemic renal injury is mediated by neutrophils and leukotrienes

Abstract

Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.

Myeloperoxidase Is Critically Involved in the Induction of Organ Damage after Renal Ischemia Reperfusion

“…[42][43][44][45] MPO specifically mediates neutrophil activation by binding to CD11b/CD18 (MAC1) integrins, 32 as well as PMN adhesion via the ␣ m ␤ 2 integrin, 33 thereby facilitating PMN extravasation. Inhibiting PMN extravasation abrogates renal I/R injury.…”

Proximal Tubule Proliferation Is Insufficient to Induce Rapid Cyst Formation after Cilia Disruption

“…7 Renal injury results in an increase in cell proliferation, particularly in the proximal tubules followed by rapid cyst development. It is important to note that in addition to proliferation, renal injury causes epithelial dedifferentiation, increased cell death, and inflammation, [13][14][15][16] other factors that may enhance cyst formation.…”

Role of the Endoplasmic Reticulum Unfolded Protein Response in Glomerular Epithelial Cell Injury

“…In addition to complement, other types of stress may injure GEC. For example, during or after renal ischemia-reperfusion injury there is up-regulation of glomerular heat shock and ER stress proteins, activation of nitric-oxide synthases, glomerular infiltration with leukocytes, and development of sclerosis (23)(24)(25)(26)(27).…”