Anti-P-selectin antibody attenuates rat brain ischemic injury

Suzuki, Hitoshi; Hayashi, Takeshi; Tojo, Shinichiro J.; Kitagawa, Hisashi; Kimura, Katsuhiko; Mizugaki, Michinao; Itoyama, Yasuto; Abe, Kōji

doi:10.1016/s0304-3940(99)00229-3

Cited by 62 publications

(34 citation statements)

References 17 publications

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“…P-selectin blockade has been observed to reduce brain injury induced by permanent middle cerebral artery occlusion (33). Furthermore, direct observation of the cerebral microcirculation has revealed a critical role for P-selectin in short-term models, such as exposure to nicotine, systemic TNF-␣, and LPS (15,34,35).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

James

Bullard

Hickey

2003

The Journal of Immunology

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MRL/faslpr mice are affected by a systemic autoimmune disease that results in leukocyte recruitment to a wide range of vascular beds, including the cerebral microvasculature. The mechanisms responsible for the leukocyte trafficking to the brain in these animals are not known. Therefore, the aim of this study was to directly examine the cerebral microvasculature in MRL/faslpr mice and determine the molecular mechanisms responsible for this leukocyte recruitment. Intravital microscopy was used to assess leukocyte-endothelial cell interactions (rolling, adhesion) in the pial microcirculation of MRL+/+ (control) and MRL/faslpr mice at 8, 12, and 16 wk of age. Leukocyte rolling and adhesion were rarely observed in MRL+/+ mice of any age. MRL/faslpr mice displayed similar results at 8 and 12 wk. However, at 16 wk, significant increases in leukocyte rolling and adhesion were observed in these mice. Histological analysis revealed that the interacting cells were exclusively mononuclear. Leukocyte rolling was reduced, but not eliminated in P-selectin−/−-MRL/faslpr mice. However, leukocyte adhesion was not reduced in these mice, indicating that P-selectin-dependent rolling was not required for leukocyte recruitment to the cerebral vasculature in this model of systemic inflammation. E-selectin blockade also had no effect on leukocyte rolling. In contrast, blockade of either the α4 integrin or VCAM-1 eliminated P-selectin-independent leukocyte rolling. α4 Integrin blockade also significantly inhibited leukocyte adhesion. These studies demonstrate that the systemic inflammatory response that affects MRL/faslpr mice results in leukocyte rolling and adhesion in the cerebral microcirculation, and that the α4 integrin/VCAM-1 pathway plays a central role in mediating these interactions.

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Section: Discussionmentioning

confidence: 99%

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

James

Bullard

Hickey

2003

The Journal of Immunology

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“…Furthermore, in vitro studies under flow have shown that platelets express the LFA-1 ligand ICAM-2 and the chemokine RANTES (CCL5) on their surfaces (87)(88)(89), which led to platelet-dependent PSGL-1, CCR1/CCR5, and LFA-1-dependent recruitment on the brain endothelium, which appears to lack these signals. A dominant role for P-selectin in leukocyte recruitment has been reported in a number of models of brain inflammation including traumatic brain injury (90), permanent middle cerebral artery occlusion (91), and other inflammatory conditions (84), but not in some models of multiple sclerosis, where ␣ 4 -integrin was more important for mononuclear cell recruitment (92).…”

Section: Organ-specific Recruitmentmentioning

confidence: 99%

The Physiology of Leukocyte Recruitment: An In Vivo Perspective

Petri

Phillipson

Kubes

2008

The Journal of Immunology

233

199

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The mechanisms of leukocyte recruitment have been studied extensively in vitro and have shed light on the basic molecular structure-function relationship of adhesion and signaling molecules involved in this essential immune response. This review will summarize how these in vitro observations extend to leukocyte behavior in inflamed blood vessels in the microcirculation. We highlight physiological results that might not have been predicted from in vitro systems. Special attention is placed on the physiology of rolling, adhesion, and intralumenal crawling in blood vessels. The importance of the glycocalyx, secondary tethers, shear, and the microenvironment are discussed. Docking structures forming rings of adhesion molecules together with a novel endothelial dome-like structure in vivo during transmigration are highlighted. Transcellular and paracellular emigration out of inflamed blood vessels is also discussed. The last section highlights leukocyte recruitment in some organs that do not always follow the accepted paradigm of leukocyte recruitment.

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“…Once exposed on activated platelets, P-selectin on platelets interacts with leukocytes and then induces inflammatory signals to potentiate vascular injury (7,8). In several experimental studies (9,10), early manipulation for P-selectin attenuates the reperfusion injury and infarction volume in ischemic rat brain, suggesting that P-selectin on platelets may implicate in progression of ischemic stroke. Actually, it has been reported that the surface expression of P-selectin on platelets is significantly increased in patients with acute ischemic stroke compared to normal control (11,12).…”

Section: Introductionmentioning

confidence: 99%

“…In animal studies, P-selectin accumulates neutrophils in the ischemic brain and eventually leads to brain edema (9,10). Therefore, it is hypothesized that overexpression of P-selectin on platelets may aggravate the progress of ischemic stroke.…”

mentioning

confidence: 99%

Surface Expression of P-selectin on Platelets Is Related with Clinical Worsening in Acute Ischemic Stroke

et al. 2002

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Platelet activation has a critical role in arterial disorders. In this study, we showed that the upregulation of P-selectin expression on platelets was related with clinical worsening in acute ischemic stroke. We serially (within 24 hr, at 72 hr, and 7 days) measured the expression of P-selectin on platelets in patients with acute ischemic stroke (n=45) and investigated the correlation between their extents and clinical severity of ischemic stroke. A significant relationship between the P-selectin expressions and National Institute of Health Stroke Scale (NIHSS) was observed at 72 hr and 7 days after ischemic stroke onset. Patients with clinical deterioration showed significantly increased expression of P-selectin on platelets as compared to those without deterioration. These results suggest that the P-selectin expression on platelets may contribute to the aggravation of clinical course in acute ischemic stroke. Thus, adequate manipulation of activated platelets is an important therapeutic strategy in acute ischemic stroke.

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Anti-P-selectin antibody attenuates rat brain ischemic injury

Cited by 62 publications

References 17 publications

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

The Physiology of Leukocyte Recruitment: An In Vivo Perspective

Surface Expression of P-selectin on Platelets Is Related with Clinical Worsening in Acute Ischemic Stroke

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