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

PloS One
Cynthia L BristowRonald Winston

Abstract

The 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. Active α(1)PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4(+) lymphocytes were correlated with the combined factors α(1)PI, HLE(CS) (+) lymphocytes, and CXCR4(+) lymphocytes (r(2) = 0.91, p<0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/µl, CD4(+) lymphocytes were correlated solely with active α(1)PI (r(2) = 0.93, p<0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient bl...Continue Reading

Associated Clinical Trials

Nov 22, 2012·Cynthia L Bristow, PhDCynthia L Bristow, PhD

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Citations

May 31, 2012·Journal of Visualized Experiments : JoVE·Cynthia L BristowRonald Winston
Mar 12, 2016·Expert Opinion on Therapeutic Patents·Yotam LiorEli C Lewis
Apr 14, 2016·Journal of Proteomics·Elisabetta GianazzaIvano Eberini
Apr 25, 2015·Revue des maladies respiratoires·J TracletJ-F Mornex
Aug 31, 2018·HIV Medicine·R F ThudiumUNKNOWN Copenhagen Co-morbidity in HIV Infection (COCOMO) Study Group
Aug 29, 2013·Stem Cells Translational Medicine·Gregory G BurrowsRichard T Maziarz

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Datasets Mentioned

BETA
BT019455

Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

SigmaPlot
FlowJo
Cn3D
Adobe Photoshop

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