Human NK Cells Expressing α4β1/β7 Adhere to VCAM‐1 Without Preactivation

Pinola, Mari; Saksela, Eero; Tiisala, Sinikka; Renkonen, Risto

doi:10.1111/j.1365-3083.1994.tb03351.x

Cited by 13 publications

(3 citation statements)

References 33 publications

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“…CD16 + Natural Killer cells, which are important in early stages of immune responses, constitutively bind soluble VCAM-1 with high affinity (52). This could explain spontaneous NK cell adhesion to immobilized VCAM-1 (55). Maximal rates of cell migration occur on lower substrate densities when integrin affinity for ligand is increased (56).…”

Section: Affinity Regulationmentioning

confidence: 99%

Integrin Activation

Woodside¹,

Liu²,

Ginsberg³

2001

Thromb Haemost

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SummaryIntegrins are cell surface adhesion receptors that participate in a variety of important processes throughout the vasculature. Here we summarize some recent findings on the regulation of integrin mediated cellular adhesion. Particular emphasis is placed on the regulation of integrin affinity for ligand (activation), although this is just one mechanism by which regulation of integrin-dependent cell adhesion can occur. Also discussed are recent observations on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand binding domain.

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Section: Affinity Regulationmentioning

confidence: 99%

Integrin Activation

Woodside¹,

Liu²,

Ginsberg³

2001

Thromb Haemost

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“…These effects require cell-cell contact and occur independently of IgG XNA, although in the presence of antibody the activation stimulus is increased by secretion of TNFα and IFNγ. Although human IFNγ has no effect on porcine cells [76], human TNFα will stimulate pig endothelial cells to up-regulate expression of adhesion molecules [77], two of which, ICAM-1 and VCAM are important for the transmigration of NK cells [78][79][80][81]. Attempts to block this transmigration, using pig-specific monoclonal antibodies, may be particularly useful to prevent the influx of inflammatory cells into a xenograft [220].…”

Section: Delayed Xenograft Rejectionmentioning

confidence: 99%

Strategies for preventing porcine xenograft rejection: recent progress and future developments

Dorling¹

1997

Expert Opinion on Therapeutic Patents

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“…[79][80][81] PML may infiltrate xenografts more rapidly than NK cells and Tcells because they adhere to P-selectin, [82][83][84][85] unlike NK cells, which utilize ICAM-1, VCAM-1 and possibly E-selectin. 61,86,87 Human neutrophils have been shown to directly recognize xenogeneic endothelium. 81 The implication that neutrophils participate in xenograft rejection is further strengthened by immunohistological studies that show significant infiltrates of leukocytes consisting predominantly of neutrophils, macrophages, and T cells, with occasional B cells and NK cells in the setting of porcine hyperacute rejection.…”

Section: Polymorphonuclear Leukocytesmentioning

confidence: 99%

Factors in Xenograft Rejection

Robson

Esch

Bach

1999

Annals of the New York Academy of Sciences

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Important mechanisms underlying immediate xenograft loss by hyperacute rejection (HAR), in the pig-to-primate combination, have been recently delineated. There are now several proposed therapies that deal with the problem of complement activation and xenoreactive natural antibody (XNA) binding to the vasculature that have been shown to prevent HAR. However, vascularized xenografts are still lost, typically within days, by delayed xenograft rejection (DXR), alternatively known as acute vascular rejection (AVR). This process is characterized by endothelial cell (EC) perturbation, localization of XNA within the graft vasculature, host NK cell and monocyte activation with platelet sequestration and vascular thrombosis. Alternative immunosuppressive strategies, additive anti-complement therapies with the control of any resulting EC activation processes and induction of protective responses have been proposed to ameliorate this pathological process. In addition, several potentially important molecular incompatibilities between activated human coagulation factors and the natural anticoagulants expressed on porcine EC have been noted. Such incompatibilities may be analogous to cross-species alterations in the function of complement regulatory proteins important in HAR. Disordered thromboregulation is potentially relevant to the progression of inflammatory events in DXR and the disseminated intravascular coagulation seen in primate recipients of porcine renal xenografts. We have recently demonstrated the inability of porcine tissue factor pathway inhibitor (TFPI) to adequately neutralize human factor Xa (FXa), the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant, thrombomodulin to bind human thrombin and hence activate human protein C. The enhanced potential of porcine von Willebrand factor to associate with human platelet GPIb has been demonstrated to be dependent upon the isolated A1 domain of von Willebrand factor. In addition, the loss of TFPI and vascular ATPDase/CD39 activity following EC activation responses would potentiate any procoagulant changes within the xenograft. These developments could exacerbate vascular damage from whatever cause and enhance the activation of platelets and coagulation pathways within xenografts resulting in graft infarction and loss. Analysis of these and the other putative factors underlying DXR should lead to the development and testing of genetic approaches that, in conjunction with selected pharmacological means, may further prolong xenograft survival to a clinically relevant extent.

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Human NK Cells Expressing α4β1/β7 Adhere to VCAM‐1 Without Preactivation

Cited by 13 publications

References 33 publications

Integrin Activation

Integrin Activation

Strategies for preventing porcine xenograft rejection: recent progress and future developments

Factors in Xenograft Rejection

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