Neutrophil-Mediated Damage to Vascular Endothelium in the Spontaneously Hypertensive Rat

Ofosu‐Appiah, William; Sfeir, George; Smith, Daniel J.; Richard, Todd A.

doi:10.1006/clin.1997.4361

Cited by 24 publications

(17 citation statements)

References 20 publications

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“…We found that SHR plasma had enhanced MMP activities, which contributes to the reduction of an ICAM-1 receptor, CD18, and probably ICAM-1 itself, based on the current results [28,29]. In vitro, neutrophils isolated from SHRs induced damage to activated endothelial cells by elastase upon direct cellular contact while isolated medium has no effect [14]. In agreement with these observations, our results showed that elastase activity on the surface of neutrophils is increased in SHRs, while elastase activity in plasma is negligible.…”

Section: Discussionmentioning

confidence: 65%

“…ICAM-1 is a key mediator of leukocyte recruitment in various diseases involving leukocyte-induced tissue injuries [11,12,13]. Likewise, SHR neutrophils can damage activated endothelial cells expressing ICAM-1, and the damage is alleviated by inhibiting ICAM-1-mediated cell adhesion [14]. Antihypertensive drugs such as amlodipine and hydralazine have been shown to reduce leukocyte migration in SHRs, which is accompanied by decreased ICAM-1 expression on vascular endothelium [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

et al. 2011

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Background/Aims: Leukocyte adhesion to the endothelium is abnormal in hypertension. We have recently shown that spontaneously hypertensive rats (SHRs) have circulating leukocytes with enhanced CD18 receptor cleavage. In the current study, we investigate expression levels of its counter receptor, intercellular adhesion molecule (ICAM-1), and its possible proteolytic cleavage in the SHR and control Wistar rat. Methods: ICAM-1 was labeled on tissue sections with two antibodies targeting its extracellular and intracellular domains and evaluated by light absorption measurements. The in situ cleavage of ICAM-1 was assessed by treating vessel sections with matrix metalloproteinase (MMP)-7, MMP-9 and elastase. Results: SHRs showed a significant increase in ICAM-1 expression in liver and kidney compared with Wistar rats. The liver and kidney glomeruli exhibit a discrepancy in label density between intra- and extracellular antibodies, which suggests that enzymatic cleavage may be a factor determining ICAM-1 distribution. MMP-7 and MMP-9, which are elevated in SHR plasma, and elastase, which has elevated activity in SHR neutrophils, cleave the extracellular domain of ICAM-1 when applied to the tissue. Conclusion: ICAM-1 expression in SHRs is upregulated in a tissue-specific manner. Proteolytic cleavage of the extracellular domain of ICAM-1 and accumulation in kidney glomeruli may play a role in the renal involvement of inflammation.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

et al. 2011

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“…9,10 Studies have also colocalized leukocytes with dead and dying endothelial cells in the diabetic retina. 4 However, the primacy of leukocytes in the development of diabetic retinal endothelial cell death is in doubt.…”

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confidence: 99%

Leukocyte-Mediated Endothelial Cell Injury and Death in the Diabetic Retina

Joussen

Murata

Tsujikawa

et al. 2001

The American Journal of Pathology

509

394

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Endothelial cell death is a hallmark of diabetic retinopathy. Its occurrence is required for the formation of acellular (devitalized) capillaries, lesions that produce irreversible retinal ischemia through their inability to support blood flow. The mechanisms underlying diabetic retinal endothelial cell injury and death remain largely unknown. The current study demonstrates that adherent leukocytes are temporally and spatially associated with retinal endothelial cell injury and death within 1 week of streptozotocin-induced experimental diabetes in rats. Moreover, the antibody-based neutralization of intercellular adhesion molecule-1 and CD18 is shown to prevent both leukocyte adhesion and retinal endothelial cell injury and death. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-intercellular adhesion molecule1-and anti-CD18-based therapies in the treatment of diabetic retinopathy, a newly recognized inflammatory disease.

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“…There is evidence suggesting that PMN are involved in the pathogenesis of sepsis and multiple organ dysfunction syndrome (12,25,30,35). Release of interleukin-8 (IL-8), which is strongly chemotactic for PMN and induces the expression of adhesion molecules on endothelial cells, may encourage activated PMN to adhere to endothelial cells, thereby inducing endothelial damage (1,10,21,33,51). However, other agonists, such as C5a, activated factor XII (FXIIa), or kallikrein, may be involved as well (15,18,38,41,48,49).…”

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confidence: 99%

Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis

Zeerleder

Caliezi

Mierlo

et al. 2003

Clin Vaccine Immunol

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Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-␣ 1 -antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.

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Neutrophil-Mediated Damage to Vascular Endothelium in the Spontaneously Hypertensive Rat

Cited by 24 publications

References 20 publications

Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

Leukocyte-Mediated Endothelial Cell Injury and Death in the Diabetic Retina

Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis

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