Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils

Abstract

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.

Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.

“…Neutrophils accumulate in various organs after ischemia and reperfusion (27)(28)(29). Neutrophil depletion has been shown to protect rats against ischemic renal injury in some studies (29,30) but not in others (31,32).…”

“…Neutrophil depletion has been shown to protect rats against ischemic renal injury in some studies (29,30) but not in others (31,32). These studies varied with regard to the model of ischemia used, the measure of renal function, the age and gender of the animals, and, perhaps most importantly, the degree of neutropenia achieved.…”

Role of Protein C in Renal Dysfunction after Polymicrobial Sepsis

“…Moreover, CXCL1 seems to be a useful biomarker for renal injury in both rodent models and humans (14). In both humans and model systems, the accumulation of leukocytes has been well demonstrated during ARF (15,16), and activated leukocytes can initiate an inflammatory cascade that leads to endothelial cell injury and disruption of the endothelial permeability barrier, thereby contributing to renal injury (17).…”

Oxidative and Nitrosative Stress in the Ischemic Acute Renal Failure

“…Renal ischemia/reperfusion is accompanied by a persistent reduction in renal blood flow of greater magnitude in the outer medulla. Mechanisms involved in this persistent reduction in renal perfusion are incompletely understood, but it has been observed endothelial cell swelling and detachment with trapping of red blood cells and leukocytes that produce vascular congestion of renal microcirculation especially in outer medulla (Olof et al, 1991;Hellberg et al, 1990aHellberg et al, , 1990bMason et al, 1984;Solez et al, 1974). Endothelial dysfunction in the outer medulla could contribute to the tubular epithelial cell injury thus determining a progressive fall in glomerular filtration rate in the initial and extending phases of acute renal failure.…”