Intercellular adhesion molecule-1 deficiency prolongs survival and protects against the development of pulmonary inflammation during murine lupus.

Lloyd, Clare M.; Gonzalo, José-Ángel; Salant, David J.; Just, John J.; Gutierrez‐Ramos, José Carlos

doi:10.1172/jci119647

Cited by 51 publications

(34 citation statements)

References 34 publications

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“…For example, ICAM-1 neutralizing antibody blocks cell-associated human immunodeficiency virus type 1 transmission across a cervical epithelial monolayer (4). Modulating ICAM-1 signaling may also alleviate the outcomes of many diseases, such as colonic inflammation, asthma, and polymicrobial sepsis (1,11,12,19,23,31). Our current findings support an important role of ICAM-1 in WNV neuroinvasion and also suggest the potential application of modulating ICAM-1 signaling in controlling the pathogenesis of West Nile encephalitis and other neuroinvasive flaviviral infections.…”

supporting

confidence: 73%

ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System

Dai

Wang²,

Bai³

et al. 2008

J Virol

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Determining how West Nile virus crosses the blood-brain barrier is critical to understanding the pathogenesis of encephalitis. Here, we show that ICAM-1 ؊/؊ mice are more resistant than control animals to lethal West Nile encephalitis. ICAM-1 ؊/؊ mice have a lower viral load, reduced leukocyte infiltration, and diminished neuronal damage in the brain compared to control animals. This is associated with decreased blood-brain barrier leakage after viral infection. These data suggest that ICAM-1 plays an important role in West Nile virus neuroinvasion and that targeting ICAM-1 signaling may help control viral encephalitis.

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supporting

confidence: 73%

ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System

Dai

Wang²,

Bai³

et al. 2008

J Virol

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“…Our careful analyses of renal function (BUN and albuminuria) allow us to state with assuredness that none of the ten complement-inhibited animals that died spontaneously did so from renal disease. Clearly there are other organ systems involved in lupus mice (20,30), as is true in the human disease.…”

Section: Discussionmentioning

confidence: 99%

Administration of a Soluble Recombinant Complement C3 Inhibitor Protects Against Renal Disease in MRL/lpr Mice

Bao

Haas²,

Kraus³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Complement receptor 1-related gene/protein y (Crry) in rodents is a potent membrane complement regulator that inhibits complement C3 activation by both classical and alternative pathways. To clarify the role of complement in lupus nephritis, MRL/lpr mice were given Crry as a recombinant protein (Crry-Ig) from 12 to 24 wk of age. Control groups were given saline or normal mouse IgG. Sera and urine were collected biweekly. Only 1 of 20 (5%) Crry-Ig-treated mice developed renal failure (BUN Ͼ 50 mg/dl) compared with 18 of 38 (47.4%) mice in control groups (P ϭ 0.001). BUN levels at 24 wk were reduced from 68.8 Ϯ 9.7 mg/dl in control groups to 38.5 Ϯ 3.9 mg/dl in the Crry-Ig-treated group (P Ͻ 0.01). Urinary albumin excretion at 24 wk was also significantly reduced from 5.3 Ϯ 1.4 mg/mg creatinine in the control groups to 0.5 Ϯ 0.2 mg/mg creatinine in the Crry-Ig-treated group (P Ͻ 0.05). Of the histologic data at 24 wk, there was a significant reduction in scores for glomerulosclerosis and C3d, IgG, IgG3, and IgA staining intensity in glomeruli in complement-inhibited animals. Crry-Ig-treated animals were also protected from vasculitic lesions. Although there was no effect on relevant autoimmune manifestations such as anti-double stranded DNA titers or cryoglobulin IgG3 levels, circulating immune complex levels were markedly higher in complement-inhibited animals. Thus, inhibition of complement activation with Crry-Ig significantly reduces renal disease in MRL/lpr lupus mice. The data support the strategy of using recombinant complement C3 inhibitors to treat human lupus nephritis.

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“…Yet, this conclusion came into question from studies by Lloyd et al (36) with MRL/lpr mice with targeted deficiency of ICAM-1. Their results suggested that pulmonary disease led to mortality in MRL/lpr mice; this was delayed in ICAM-1-deficient animals.…”

Section: Discussionmentioning

confidence: 99%

Transgenic Expression of a Soluble Complement Inhibitor Protects Against Renal Disease and Promotes Survival in MRL/lprMice

Bao

Haas

Boackle

et al. 2002

The Journal of Immunology

105

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To investigate the role of complement in lupus nephritis, we used MRL/lpr mice and a transgene overexpressing a soluble complement regulator, soluble CR1-related gene/protein y (sCrry), both systemically and in kidney. Production of sCrry in sera led to significant complement inhibition in Crry-transgenic mice relative to littermate transgene negative controls. This complement inhibition with sCrry conferred a survival advantage to MRL/lpr mice. In a total of 154 animals, 42.5% transgene-negative animals had impaired renal function (blood urea nitrogen > 50 mg/dl) compared with 16.4% mice with the sCrry-producing transgene (p < 0.001). In those animals that died spontaneously, MRL/lpr mice with the sCrry-producing transgene did not die of renal failure, while those without the transgene did (blood urea nitrogen values of 46.6 ± 9 and 122 ± 29 mg/dl in transgene-positive and transgene-negative animals, respectively; p < 0.001). Albuminuria was reduced in those transgenic animals in which sCrry expression was maximally stimulated (urinary albumin/creatinine = 12.4 ± 4.3 and 36.9 ± 7.7 in transgene-positive and transgene-negative animals, respectively; p < 0.001). As expected in the setting of chronic complement inhibition, there was less C3 deposition in glomeruli of sCrry-producing transgenic mice compared with transgene-negative animals. In contrast, there was no effect on glomerular IgG deposition, levels of anti-dsDNA Ab and rheumatoid factor, or spleen weights between the two groups. Thus, long-term complement inhibition reduces renal disease in MRL/lpr mice, which translates into improved survival. MRL/lpr mice in which complement is inhibited still have spontaneous mortality, yet this is not from renal disease.

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Intercellular adhesion molecule-1 deficiency prolongs survival and protects against the development of pulmonary inflammation during murine lupus.

Cited by 51 publications

References 34 publications

ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System

ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System

Administration of a Soluble Recombinant Complement C3 Inhibitor Protects Against Renal Disease in MRL/lpr Mice

Transgenic Expression of a Soluble Complement Inhibitor Protects Against Renal Disease and Promotes Survival in MRL/lprMice

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