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J Allergy Clin Immunol. 2007 Feb;119(2):457-63. Epub 2006 Dec 4.

Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus.

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  • 1Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

Erratum in

  • J Allergy Clin Immunol. 2008 Nov;122(5):1007.. Kisich, Kevin [added].

Abstract

BACKGROUND:

Patients with atopic dermatitis (AD) are prone to disseminated viral skin infections and therefore are not vaccinated against smallpox because of potential complications. Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown.

OBJECTIVE:

Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV).

METHODS:

Macrophage inflammatory protein 3alpha levels were evaluated using real-time RT-PCR, immunodot-blot, and immunohistochemistry. The antiviral activity of MIP-3alpha was determined using a standard viral plaque assay.

RESULTS:

Macrophage inflammatory protein 3alpha gene expression was significantly (P < .01) decreased in AD skin (0.21 +/- 0.05 ng MIP-3alpha/ng glyceraldehyde-3-phosphate dehydrogenase) compared with psoriasis skin (0.67 +/- 0.13). This was confirmed at the protein level using immunohistochemistry. We further demonstrate that T(H)2 cytokines downregulate MIP-3alpha expression. The importance of MIP-3alpha in the innate immune response against VV was established by first demonstrating that MIP-3alpha exhibits activity against VV. Second, VV replication was significantly increased (P < .01) in keratinocytes treated with an antibody to neutralize MIP-3alpha.

CONCLUSION:

The current study demonstrates that MIP-3alpha exhibits antiviral activity against VV and demonstrates the importance of MIP-3alpha in the innate immune response against VV. In addition, AD skin is deficient in MIP-3alpha, in part because of the overexpression of T(H)2 cytokines in AD skin.

CLINICAL IMPLICATIONS:

MIP-3alpha deficiency in AD skin contributes to patients' increased propensity toward eczema vaccinatum. Increasing MIP-3alpha or neutralizing T(H)2 cytokines could prevent adverse reactions in patients with AD after smallpox vaccination.

PMID:
17141855
[PubMed - indexed for MEDLINE]
PMCID:
PMC2746067
Free PMC Article
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