Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome.

Abstract

Wiskott-Aldrich syndrome (WAS) is a rare disease characterized by microthrombocytopenia, eczema and immune deficiency. In this study a direct-viewing chemotaxis chamber was used to analyse chemotactic responses of WAS neutrophils and macrophages in stable linear concentration gradients. In five patients with classic WAS, chemotaxis of macrophages but not of neutrophils was found to be abolished, whereas the speed of random motility of both cell types was found to be indistinguishable from control cells. This supports the existence of an essential functional link, previously suggested by biochemical studies, between Cdc42, WAS protein (WASp) and the actin cytoskeleton in primary human macrophages. Moreover, these data suggest that Cdc42-WASp-mediated filopodial extension is a requirement for chemotaxis but not for chemokinesis in these cells. Abnormal directional cell motility of macrophages and related antigen-presenting cells may play a significant part in the immune deficiency and eczema of WAS.

Full text links

Read article at publisher's site: https://doi.org/10.1046/j.1365-2141.1998.00767.x

Read article for free, from open access legal sources, via Unpaywall: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2141.1998.00767.x

References

Articles referenced by this article (43)

Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages.
Allen WE, Jones GE, Pollard JW, Ridley AJ
J Cell Sci, 707-720 1997
MED: 9099945
Abnormalities of chemotactic lymphokine synthesis and mononuclear leukocyte chemotaxis in Wiskott-Aldrich syndrome.
Altman LC, Snyderman R, Blaese RM
J Clin Invest, (2):486-493 1974
MED: 4136226
Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome.
Aspenstrom P, Lindberg U, Hall A
Curr Biol, (1):70-75 1996
MED: 8805223
Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases.
Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I
Curr Biol, (8):981-988 1996
MED: 8805332
Colony-stimulating factor-1 induces rapid behavioural responses in the mouse macrophage cell line, BAC1.2F5.
Boocock CA, Jones GE, Stanley ER, Pollard JW
J Cell Sci, 447-456 1989
MED: 2532650
Identification of Itk/Tsk Src homology 3 domain ligands.
Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ
J Biol Chem, (41):25646-25656 1996
MED: 8810341
Title not supplied
AUTHOR UNKNOWN
Wiskott-Aldrich syndrome. An immunologic deficiency disease involving the afferent limb of immunity.
Cooper MD, Chae HP, Lowman JT, Krivit W, Good RA
Am J Med, (4):499-513 1968
MED: 4171085
Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways.
Cory GO, MacCarthy-Morrogh L, Banin S, Gout I, Brickell PM, Levinsky RJ, Kinnon C, Lovering RC
J Immunol, (9):3791-3795 1996
MED: 8892607
Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.
Derry JM, Ochs HD, Francke U
Cell, (4):635-644 1994
MED: 8069912

Show 10 more references (10 of 43)

Citations & impact

Impact metrics

147

Citations

Jump to Citations

Citations of article over time

Article citations

ARP2/3 complex associates with peroxisomes to participate in pexophagy in plants.
Martinek J, Cifrová P, Vosolsobě S, García-González J, Malínská K, Mauerová Z, Jelínková B, Krtková J, Sikorová L, Leaves I, Sparkes I, Schwarzerová K
Nat Plants, 9(11):1874-1889, 16 Oct 2023
Cited by: 4 articles | PMID: 37845336
A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing.
Rodríguez-Fernández JL, Criado-García O
Front Immunol, 13:1001086, 20 Oct 2022
Cited by: 1 article | PMID: 36341452 | PMCID: PMC9630654
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.
Yuan B, Zhou X, Suzuki K, Ramos-Mandujano G, Wang M, Tehseen M, Cortés-Medina LV, Moresco JJ, Dunn S, Hernandez-Benitez R, Hishida T, Kim NY, Andijani MM, Bi C, Ku M, Takahashi Y, Xu J, Qiu J, Huang L, [...] Li M
Nat Commun, 13(1):3646, 25 Jun 2022
Cited by: 6 articles | PMID: 35752626 | PMCID: PMC9233711
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells.
Leung G, Zhou Y, Ostrowski P, Mylvaganam S, Boroumand P, Mulder DJ, Guo C, Muise AM, Freeman SA
JCI Insight, 6(23):e149376, 08 Dec 2021
Cited by: 9 articles | PMID: 34673575 | PMCID: PMC8675194
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
WASp controls oriented migration of endothelial cells to achieve functional vascular patterning.
Rosa A, Giese W, Meier K, Alt S, Klaus-Bergmann A, Edgar LT, Bartels-Klein E, Collins RT, Szymborska A, Coxam B, Bernabeu MO, Gerhardt H
Development, 149(3):dev200195, 01 Feb 2022
Cited by: 9 articles | PMID: 34931661 | PMCID: PMC8918813
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC

Go to all (147) article citations

Funding

Funders who supported this work.

Search life-sciences literature (45,100,050 articles, preprints and more)

Affiliations

ORCIDs linked to this article

Abstract

Full text links

References

Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages.

Abnormalities of chemotactic lymphokine synthesis and mononuclear leukocyte chemotaxis in Wiskott-Aldrich syndrome.

Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases.

Colony-stimulating factor-1 induces rapid behavioural responses in the mouse macrophage cell line, BAC1.2F5.

Identification of Itk/Tsk Src homology 3 domain ligands.

Title not supplied

Wiskott-Aldrich syndrome. An immunologic deficiency disease involving the afferent limb of immunity.

Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways.

Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.

Citations & impact

Impact metrics

Citations of article over time

Article citations

ARP2/3 complex associates with peroxisomes to participate in pexophagy in plants.

A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing.

Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing.

ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells.

WASp controls oriented migration of endothelial cells to achieve functional vascular patterning.

Similar Articles

Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp.

The chemotactic defect in wiskott-Aldrich syndrome macrophages is due to the reduced persistence of directional protrusions.

Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation.

Macrophages of patients with X-linked thrombocytopenia display an attenuated Wiskott-Aldrich syndrome phenotype.

Funding

Wellcome Trust

Partnerships & funding

Search life-sciences literature (45,100,050 articles, preprints and more)

Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome.

Author information

Affiliations

ORCIDs linked to this article

Abstract

Full text links

References

Title not supplied

Citations & impact

Impact metrics

Citations of article over time

Article citations

Similar Articles

Funding

Wellcome Trust

Partnerships & funding