PLoS ONE (Jan 2012)

α1Proteinase inhibitor regulates CD4+ lymphocyte levels and is rate limiting in HIV-1 disease.

  • Cynthia L Bristow,
  • Mariya A Babayeva,
  • Michelle LaBrunda,
  • Michael P Mullen,
  • Ronald Winston

DOI
https://doi.org/10.1371/journal.pone.0031383
Journal volume & issue
Vol. 7, no. 2
p. e31383

Abstract

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BackgroundThe regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE(CS)), it acts not as a proteinase, but as a receptor for α(1)proteinase inhibitor (α(1)PI, α(1)antitrypsin, SerpinA1). Binding of α(1)PI to HLE(CS) forms a motogenic complex. We previously demonstrated that α(1)PI deficiency attends HIV-1 disease and that α(1)PI augmentation produces increased numbers of immunocompetent circulating CD4(+) lymphocytes. Herein we investigated the mechanism underlying the α(1)PI deficiency that attends HIV-1 infection.Methods and findingsActive α(1)PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p220 CD4 cells/µl, CD4(+) lymphocytes were correlated solely with active α(1)PI (r(2) = 0.93, pConclusionsThis report identifies an autoimmune component of HIV-1 disease that can be overcome therapeutically. Importantly, results identify an achievable vaccine modification with the novel objective to protect against AIDS as opposed to the current objective to protect against HIV-1 infection.