Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.

Mulligan, Michael S.; Johnson, Kent J.; Todd, rd R F; Issekutz, Thomas B.; Miyasaka, Masayuki; Tamatani, Takuya; Smith, C. W.; Anderson, D. C.; Ward, Peter A.

doi:10.1172/jci116237

Cited by 189 publications

(113 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of TNF resulted in a significant inhibition of renal injury, as shown by a >50% reduction in urinary albumin: creatinine ratio (Fig. 7C), consistent with previously published results in similar models (31,32). Similarly, inhibition of CXCL1 also resulted in a significant reduction in urinary albumin: creatinine ratio (Fig.…”

Section: Tnf Is Up-regulated In Monocytes In the Inflamed Kidney Andsupporting

confidence: 91%

“…Of these mediators, TNF has been previously identified as a critical mediator in in situ immune complexmediated glomerulonephritis, via its promotion of adhesion molecule expression and glomerular barrier breakdown (31,32). TNF is also a potent and rapid inducer of ROS production via stimulation of NAPDH oxidase activity in neutrophils (39), a pathway we have previously shown to be responsible for glomerular dysfunction in acute glomerular inflammation (20).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Finsterbusch

Hall

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

139

View full text Add to dashboard Cite

Nonclassical monocytes undergo intravascular patrolling in blood vessels, positioning them ideally to coordinate responses to inflammatory stimuli. Under some circumstances, the actions of monocytes have been shown to involve promotion of neutrophil recruitment. However, the mechanisms whereby patrolling monocytes control the actions of neutrophils in the circulation are unclear. Here, we examined the contributions of monocytes to antibody-and neutrophildependent inflammation in a model of in situ immune complexmediated glomerulonephritis. Multiphoton and spinning disk confocal intravital microscopy revealed that monocytes patrol both uninflamed and inflamed glomeruli using β 2 and α 4 integrins and CX 3 CR1. Monocyte depletion reduced glomerular injury, demonstrating that these cells promote inappropriate inflammation in this setting. Monocyte depletion also resulted in reductions in neutrophil recruitment and dwell time in glomerular capillaries and in reactive oxygen species (ROS) generation by neutrophils, suggesting a role for cross-talk between monocytes and neutrophils in induction of glomerulonephritis. Consistent with this hypothesis, patrolling monocytes and neutrophils underwent prolonged interactions in glomerular capillaries, with the duration of these interactions increasing during inflammation. Moreover, neutrophils that interacted with monocytes showed increased retention and a greater propensity for ROS generation in the glomerulus. Also, renal patrolling monocytes, but not neutrophils, produced TNF during inflammation, and TNF inhibition reduced neutrophil dwell time and ROS production, as well as renal injury. These findings show that monocytes and neutrophils undergo interactions within the glomerular microvasculature. Moreover, evidence indicates that, in response to an inflammatory stimulus, these interactions allow monocytes to promote neutrophil recruitment and activation within the glomerular microvasculature, leading to neutrophil-dependent tissue injury.monocyte-neutrophil interaction | inflammation | glomerulonephritis | reactive oxygen species | tumor necrosis factor N eutrophil recruitment is a crucial event in the response to tissue injury and host defense against pathogens. However, if dysregulated, it can also cause significant tissue injury. Inappropriate recruitment and activation of neutrophils are recognized as major contributors to organ damage in numerous inflammatory diseases, including inflammatory arthritis, acute respiratory distress syndrome, systemic lupus erythematosus, and acute glomerulonephritis (1-4). Although our understanding of the molecular basis of neutrophil recruitment is well-developed, less is known about the interactions of neutrophils with other circulating immune cells during the development of the innate inflammatory response. However, over the last decade, evidence has emerged that neutrophil recruitment and function during inflammation can be influenced by another circulating immune cell-the monocyte (5-10).Monocytes exist in two major populations,...

show abstract

Section: Tnf Is Up-regulated In Monocytes In the Inflamed Kidney Andsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Finsterbusch

Hall

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

139

View full text Add to dashboard Cite

show abstract

“…2,22,23 Several studies have shown that both platelet-derived and transforming growth factors, as well as TNF␣ may play a role in the pathogenesis of glomerular injury. 6,7,24,25 TNF␣ enhances the expression of intercellular adhesion molecule-1 (ICAM-1) 9 and blood levels of ICAM-1 were found to be increased in atherosclerotic hypertensive subjects with preserved renal function, suggesting a systemic endothelial dysfunction. 26 Furthermore, on the basis of experimental results Liu et al 27,28 hypothesised that in hypertension, vascular thrombotic risk is associated with Table 1 Mean age, serum creatinine and creatinine clearance (Clcr), blood levels of TNF␣ and ET-1, UAE, 24-h systolic-(SBP), diastolic (DBP) and mean (MBP) blood pressures in normotensive controls (NT), in patients with essential hypertension (EH), and in hypertensive subjects with renal insufficiency (CRF)…”

Section: Discussionmentioning

confidence: 99%

“…4 There is also evidence that TNF␣ may alter both glomerular haemodynamics and haemostatic balance, and induce glomerular infiltration by leukocytes. 5 TNF␣ is produced by a wide variety of cell types, mainly activated macrophages, in response to different exogenous and endogenous stimuli, and it is involved in several pathological conditions like glomerular diseases, 6,7 diabetic glomerulopathy and chronic heart failure. 8,9 Correspondence: Dr Santina Cottone Patients with hypertension manifested greater ET-1 levels than normotensive subjects (P Ͻ Ͻ Ͻ 0.01).…”

Section: Introductionmentioning

confidence: 99%

Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

et al. 1998

View full text Add to dashboard Cite

The present study was performed to compare circulating levels of tumour necrosis factor-␣ (TNF␣) and plasma endothelin 1 (ET-1), of hypertensive patients with or without renal failure and with those of normotensive healthy subjects. The study population consisted of 21 healthy normotensive subjects and 22 hypertensive patients, 11 with essential hypertension, and 11 with hypertension and chronic renal failure (CRF).Plasma ET-1 levels, serum TNF␣ and creatinine, creatinine clearance, 24-h urinary albumin excretion (UAE) were assayed, and 24-h blood pressure monitoring was obtained in all subjects. Office blood pressure was similar between hypertensive patients with and without CRF. However, 24-h blood pressure was greater in patients with CRF than in those with essential hypertension and

show abstract

“…Stimulated neutrophils likely adhere to endothelial cells via both LFA-1-ICAM-1 and Mac-1-ICAM-1 interactions (27). In other injury models [vasculitis (28) or anti-GBM (glomerular basement membrane) nephritis (29)], mAbs directed against LFA-1 have been found to be ineffective, while antibodies against ICAM-1 protect against injury.…”

mentioning

confidence: 99%

Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury.

Kelly

Williams

Colvin

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

453

236

View full text Add to dashboard Cite

The pathophysiology of ischemic acute renal failure is complex, and the role of leukocyte adhesion in this process is not well defined. A monoclonal antibody (mAb) against intracellular adhesion molecule 1 (anti-ICAM-1), administered at the time of bilateral renal ischemia in the rat, prevented both functional impairment and histologic changes of acute renal failure. Plasma creatinine measured (mg/dl) 24 hr after 30 min of ischemia was 0.61 ± 0.05 in the anti-ICAM-1-treated animals compared with 2.4 ± 0.14 (P < 0.0001) in the vehicle-treated ischemic group. Forty-eight hours after ischemia, creatinine values were 0.46 ± 0.05 and 2.03 ± 0.22 (P < 0.0001) in anti-ICAM-1 and vehicle-treated groups, respectively. A low dose of anti-ICAM-1 that was itself nonprotective, when given with partially protective doses of a mAb against lymphocyte function-associated antigen-i (anti-LFA-1), acted synergistically to prevent renal failure. Anti-ICAM-1 mAb also protected the kidney when administered 0.5 or 2 hr but not 8 hr after restoration of blood flow and when the ischemic period was extended to 40 min. Ischemia-induced increases in tissue myeloperoxidase, a marker of neutrophil infitration, were mitigated with anti-ICAM-1 treatment. Thus, anti-ICAM-1 mAb protected the kidney against ischemic renal failure, even when the antibody was administered after the ischemic period. These results suggest a critical role for leukocytes and adhesion molecules in the pathophysiology of ischemic inijury and may have important therapeutic implications.The pathophysiology of acute ischemic renal failure is poorly understood. Therapeutic interventions designed to inhibit cellular injury have frequently been either ineffective or equivocal in their effectiveness in both experimental animals and man, and rarely has an agent been effective when administered after the ischemic insult (1).We hypothesized that leukocyte adhesion plays a critical role in renal ischemia-reperfusion injury. Outer medullary vascular congestion that occurs in ischemic acute renal failure (2) may result from leukocyte-endothelial cell interactions with obstruction of the vasa recta or leukocyte-mediated increases in endothelial permeability leading to erythrocyte aggregation (3). This would sustain ischemia to the outer medulla, even if total renal blood flow were restored.Leukocyte adhesion to various cell types is mediated in large part by the three P2 integrins: CD11a/CD18 [lymphocyte function-associated antigen 1 (LFA-1)], CD11b/CD18 (Mac-i), and CD11c/CD18. The intercellular adhesion molecule 1 (ICAM-1, CD54) is a ligand for CD11a/CD18 and CD11b/CD18. The CD54-CD11/CD18 interactions are important determinants of leukocyte-endothelial cell adhesion (4). The purpose of our studies was to evaluate the effects of a monoclonal antibody (mAb) directed against ICAM-1 on ischemic acute renal failure in the rat.Ischemia results in increased tissue levels of proinflammatory mediators, including cytokines (5, 6) and products of arachidonic acid metabolism (7), which ...

show abstract

Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.

Abstract: Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. Invest. 1993. 91:577-587.)

Cited by 189 publications

References 32 publications

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Patrolling monocytes promote intravascular neutrophil activation and glomerular injury in the acutely inflamed glomerulus

Comparison of tumour necrosis factor and endothelin-1 between essential and renal hypertensive patients

Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury.

Contact Info

Product

Resources

About