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CD Markers

CD49d


Reviewers: Nat Pernick, M.D., PathologyOutlines.com (see Reviewers page)
Revised: 25 December 2010, last major update December 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

General
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● Receptor for fibronectin, thrombospondin and VCAM1/CD106

Terminology
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● Also called very late antigen (VLA) alpha 4 chain (VLA4), ITGA4

Physiology
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● Combines with CD29 to form alpha4 beta1 integrin
● Has role in cell-cell interactions, cell adhesion to the extracellular matrix
● Integrins alpha4beta1 and alpha4beta7 are receptors for fibronectin
● Integrin alpha4beta1 is also a receptor for VCAM1/CD106, MAdCAM1 and thrombospondin
● Avidity (binding strength) of cells expressing alpha4beta1 integrin can be rapidly changed by chemokines and chemoattractants
● Integrin anchorage to cytoskeleton enhances the mechanical stability of its adhesive bonds under strain and promotes its ability to mediate leukocyte adhesion under physiological shear stress conditions (J Cell Biol 2005;171:1073)
● Promotes (a) lymphocyte migration into tissue by strengthening lymphocyte adhesion to endothelial cells, (b) rolling of T cells in vascular lumen on VCAM-1 of endothelium, (c) homing of T cell subsets to Peyer's patches, (d) differentiation of hematopoietic precursor cells by adhesion to bone marrow stromal cells

Clinical features
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● Relevant to tumor progression and metastasis
● Increased expression during relapse in multiple sclerosis (J Neuroimmunol 2005;166:189); treatment with alpha4 integrin antagonist natalizumab led to fewer inflammatory brain lesions and fewer relapses in patients with relapsing MS (N Engl J Med 2003;348:15), although it is also associated with PML (Neurol Res 2006;28:299)

Uses for pathologists
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● Surface expression has prognostic signficance in CLL (Leuk Res 2010 Nov 17 [Epub ahead of print], Br J Haematol 2008;140:537)

Positive stains - normal
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● Macrophages, T and B cells, eosinophils, basophils, NK cells, dendritic cells, Langerhans cells, myeloid cells, erythrocyte precursors, thymocytes
● Also basal epidermal layer

Positive stains - disease
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● Found in suprabasal skin during wound healing and psoriasis
● Melanoma, ALL, AML

Negative stains
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● Erythrocytes, platelets, neutrophils

Additional references
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MIM 192975

End of CD Markers > CD49d


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