Calcium-Dependent Heparin-Like Ligands For L-Selectin in Nonlymphoid Endothelial Cells

Norgard-Sumnicht, Karin; Varki, Nissi; Varki, Ajit

doi:10.1126/science.7687382

Cited by 186 publications

(98 citation statements)

References 62 publications

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“…This assumption was based on in vitro and animal model data suggesting that heparin concentrations markedly below the anti-coagulative level were sufficient to block Pand L-selectin-mediated rolling (22)(23)(24)(25)(26)47). Our results argue against these suggestions, as we could document no modifications in leukocyte rolling or extravasation without concomitant alterations in the anti-coagulative status monitored with APTT.…”

Section: Discussioncontrasting

confidence: 56%

“…Heparin has been suggested to be an effective inhibitor especially of P-and to a lesser extent of Lselectin-mediated rolling and extravasation (21)(22)(23)(24)(25)(26). In allergic patients during allergen challenge, the numbers of rolling cells, with or without heparin prophylaxis were identical (Fig.…”

Section: Effect Of Heparin On Allergen-induced Leukocyte Traffic and mentioning

confidence: 99%

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Direct In Vivo Monitoring of Acute Allergic Reactions in Human Conjunctiva

Helintö

Renkonen

Tervo³

et al. 2004

The Journal of Immunology

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Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.

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Section: Discussioncontrasting

confidence: 56%

Section: Effect Of Heparin On Allergen-induced Leukocyte Traffic and mentioning

confidence: 99%

Direct In Vivo Monitoring of Acute Allergic Reactions in Human Conjunctiva

Helintö

Renkonen

Tervo³

et al. 2004

The Journal of Immunology

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“…This hypothesis was supported by the observation that heparitinase, an enzyme that speci®cally hydrolyses heparan sulfate, reduced endothelial cellassociated IL-8 immunoreactivity (Middleton et al, 1997). Additionally, heparan sulfate may also serve as counterligand for leukocyte adhesion molecules L-selectin and integrin Mac-1 (Diamond et al, 1995;Norgard-Sumnicht et al, 1993). In this view, chemokines create solid-phase rather than¯uid chemotactic gradients, acting through a process termed haptotaxis.…”

Section: Chemokines Bbb and Initiation Of Cns In¯ammationsupporting

confidence: 50%

Sentries at the gate: chemokines and the blood-brain barrier

Głąbiński¹,

Ransohoff²

1999

J Neurovirol

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“…heparin-like molecules (48,50), yet we do not observe a significant contribution of this interaction in either of our assays. In the presence of Ca 2÷ but not Mg 2+, resting neutrophils which express high levels of functional L-selectin do not interact with heparin or heparan sulfate under static or flow conditions (Fig.…”

Section: Discussionmentioning

confidence: 61%

Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD1).

Diamond

Alon

Parkos

et al. 1995

The Journal of Cell Biology

261

199

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Abstract. Previous studies have demonstrated that the leukocyte integrin Mac-1 adheres to several cell surface and soluble ligands including intercellular adhesion molecule-I, fibrinogen, iC3b, and factor X. However, experiments with Mac-l-expressing transfectants, purified Mac-l, and mAbs to Mac-1 indicate the existence of additional ligands. In this paper, we demonstrate a direct interaction between Mac-1 and heparan sulfate glycans. Heparin affinity resins immunoprecipitate Mac-l, and neutrophils and transfectant cells that express Mac-1 bind to heparin and heparan sulfate, but not to other sulfated glycosaminoglycans. Inhibition studies with mAbs and chemically modified forms of heparin suggest the I domain as a recognition site on Mac-1 for heparin, and suggest that either N-or O-sulfation is sufficient for heparin to bind efficiently to Mac-1. Under conditions of continuous flow in which heparins and E-selectin are cosubstrates, neutrophils tether to E-selectin and form firm adhesions through a Mac-l-heparin interaction.

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Calcium-Dependent Heparin-Like Ligands For L-Selectin in Nonlymphoid Endothelial Cells

Cited by 186 publications

References 62 publications

Direct In Vivo Monitoring of Acute Allergic Reactions in Human Conjunctiva

Direct In Vivo Monitoring of Acute Allergic Reactions in Human Conjunctiva

Sentries at the gate: chemokines and the blood-brain barrier

Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD1).

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