CD8+ cells in HIV infection produce macrophage inflammatory protein-1α and RANTES: a comparative study in long term survivors and progressor patients

α-Naphthylisothiocyanate (ANIT) is a hepatotoxin that causes severe neutrophilic inflammation around portal tracts and bile ducts. The chemotactic signals that provoke this inflammatory response are unknown. In this study, we addressed the possibility that ANIT upregulates CXC chemokines in the liver and that these compounds mediate hepatic inflammation and tissue injury after ANIT treatment. Mice treated with a single dose of ANIT (50 mg/kg) exhibited rapid hepatic induction of the CXC chemokine macrophage inflammatory protein-2 (MIP-2). MIP-2 derived primarily from hepatocytes, with no apparent contribution by biliary cells. In ANIT-treated mice, the induction of MIP-2 coincided with an influx of neutrophils to portal zones; this hepatic neutrophil recruitment was suppressed by 50% in mice that lack the receptor for MIP-2 (CXCR2−/−). Interestingly, despite their markedly reduced degree of hepatic inflammation, CXCR2−/− mice displayed just as much hepatocellular injury and cholestasis after ANIT treatment as wild-type mice. Moreover, after long-term exposure, ANIT CXCR2−/− mice developed liver fibrosis that was indistinguishable from that in wild-type mice. In summary, our data show that CXC chemokines are responsible for some of the hepatic inflammation that occurs in response to ANIT but that these compounds are not essential to the pathogenesis of either acute or chronic ANIT hepatotoxicity.

Download Full-text

CD34+/CD33- cells reselected from macrophage inflammatory protein 1 alpha+interleukin-3--supplemented "stroma-noncontact" cultures are highly enriched for long-term bone marrow culture initiating cells

Blood ◽

10.1182/blood.v84.5.1442.1442 ◽

1994 ◽

Vol 84 (5) ◽

pp. 1442-1449 ◽

Cited By ~ 23

Author(s):

CM Verfaillie ◽

JS Miller

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Antigen Expression ◽

Hematopoietic Stem ◽

Interleukin 3 ◽

Inflammatory Protein ◽

Hla Dr ◽

Macrophage Inflammatory Protein

Abstract Human hematopoietic stem cells are thought to express the CD34 stem cell antigen, low numbers of HLA-DR and Thy1 antigens, but no lineage commitment antigens, CD38, or CD45RA antigens. However, fluorescence- activated cell sorted CD34+ subpopulations contain not more than 1% to 5% primitive progenitors capable of initiating and sustaining growth in long-term bone marrow culture initiating cells (LTBMC-ICs). We have recently shown that culture of fresh human marrow CD34+/HLA-DR- cells separated from a stromal layer by a microporous membrane (“stroma- noncontact” culture) results in the maintenance of 40% of LTBMC-ICs. We hypothesized that reselection of CD34+ subpopulations still present after several weeks in stroma-noncontact cultures may result in the selection of cells more highly enriched for human LTBMC-ICs. Fresh marrow CD34+/HLA-DR- cells were cultured for 2 to 3 weeks in stroma- noncontact cultures. Cultured progeny was then sorted on the basis of CD34, HLA-DR, or CD33 antigen expression, and sorted cells evaluated for the presence of LTBMC-ICs by limiting dilution analysis. We show that (1) LTBMC-ICs are four times more frequent in cultured CD34+/HLA- DR- cells (4.6% +/- 1.7%) than in cultured CD34+/HLA-DR- cells (1.3% +/- 0.4%). This suggests that HLA-DR antigen expression may depend on the activation status of primitive cells rather than their lineage commitment. We then sorted cultured cells on the basis of the myeloid commitment antigen, CD33. (2) These studies show that cultured CD34+/CD33- cells contain 4% to 8% LTBMC-ICs, whereas cultured CD34+/CD33+bright cells contain only 0.1% +/- 0.03% LTBMC-ICs. Because LTBMC-ICs are maintained significantly better in stroma-noncontact cultures supplemented with macrophage inflammatory protein 1 alpha (MIP- 1 alpha) and interleukin-3 (IL-3) (Verfaillie et al, J Exp Med 179:643, 1994), we evaluated the frequency of LTBMC-ICs in CD34+/CD33- cells present in such cultures. (3) CD34+/CD33- cells present in MIP-1 alpha + IL-3-supplemented cultures contain up to 30% LTBMC-ICs. The increased frequency of LTBMC-ICs in cultured CD34+ subpopulations may be the result of terminal differentiation of less primitive progenitors, loss of cells that fail to respond to the culture conditions or recruitment of quiescent LTBMC-ICs. The capability to select progenitor populations containing up to 30% LTBMC-ICs should prove useful in studies examining the growth requirements, self-renewal, and multilineage differentiation capacity of human hematopoietic stem cells at the single-cell level.

Download Full-text

Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

Blood ◽

10.1182/blood.v81.6.1497.1497 ◽

1993 ◽

Vol 81 (6) ◽

pp. 1497-1504 ◽

Cited By ~ 33

Author(s):

VF Quesniaux ◽

GJ Graham ◽

I Pragnell ◽

D Donaldson ◽

SD Wolpe ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Inhibitory Effect ◽

In Vivo Model ◽

Hematopoietic Progenitors ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein

Abstract A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst- forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP- 1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.

Download Full-text

Neutralization of genetically diverse HIV-1 strains by IgA antibodies to the gp120–CD4-binding site from long-term survivors of HIV infection

AIDS ◽

10.1097/qad.0b013e3283376e88 ◽

2010 ◽

Vol 24 (6) ◽

pp. 875-884 ◽

Cited By ~ 21

Author(s):

Stephanie Planque ◽

Maria Salas ◽

Yukie Mitsuda ◽

Marcin Sienczyk ◽

Miguel A Escobar ◽

...

Keyword(s):

Hiv Infection ◽

Binding Site ◽

Iga Antibodies ◽

Cd4 Binding Site ◽

Long Term Survivors ◽

Hiv 1

Download Full-text

Pre-treatment of peripheral blood progenitor cells with macrophage inflammatory protein-1α induces prolonged survival of early progenitor cells over 6 weeks of long-term culture

British Journal of Haematology ◽

10.1046/j.1365-2141.1998.01105.x ◽

1998 ◽

Vol 103 (4) ◽

pp. 1181-1183 ◽

Cited By ~ 1

Author(s):

Dietmar Egger ◽

Christine Günther ◽

Werner Helbig ◽

Elisabeth Schulze

Keyword(s):

Progenitor Cells ◽

Peripheral Blood ◽

Prolonged Survival ◽

Long Term Culture ◽

Inflammatory Protein ◽

Peripheral Blood Progenitor Cells ◽

Pre Treatment ◽

Macrophage Inflammatory Protein

Download Full-text

MCP-1, not MIP-1α, Is the Endogenous Chemokine That Cooperates With TGF-β to Inhibit the Cycling of Primitive Normal but not Leukemic (CML) Progenitors in Long-Term Human Marrow Cultures

Blood ◽

10.1182/blood.v92.7.2338 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2338-2344 ◽

Cited By ~ 53

Author(s):

J.D. Cashman ◽

C.J. Eaves ◽

A.H. Sarris ◽

A.C. Eaves

Keyword(s):

Inhibitory Activity ◽

Neutralizing Antibodies ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Monocyte Chemoattractant Protein 1 ◽

Inflammatory Protein ◽

Progenitor Cell Proliferation ◽

Normal Human ◽

Macrophage Inflammatory Protein

Abstract The long-term culture (LTC) system has been useful for analyzing mechanisms by which stromal cells regulate the proliferative activity of primitive normal, but not chronic myeloid leukemia (CML), hematopoietic progenitor cells. In previous studies, we identified two endogenous inhibitors in this system. One is transforming growth factor-β (TGF-β), which is equally active on primitive normal and CML progenitors. The other we now show to be monocyte chemoattractant protein-1 (MCP-1). Thus, MCP-1, when added to LTC, blocked the activation of primitive normal progenitors but did not arrest the cycling of primitive CML progenitors. Moreover, the endogenous inhibitory activity of LTC stromal layers could be overcome by the addition of neutralizing antibodies to MCP-1, but not to macrophage inflammatory protein-1α (MIP-1α). However, neither of these antibodies antagonized the inhibitory activity of NAc-Ser-Asp-Lys-Pro (AcSDKP) on primitive normal but not CML progenitor cycling in this system. Moreover, none of six other -C-C- or -C-X-C- chemokines, previously shown to inhibit primitive normal human CFC proliferation in semisolid assays, were found to act as negative regulators when added to normal LTC. These results provide further support for the concept that primitive CML progenitor cell proliferation is deregulated when these cells are exposed to limiting concentrations of multiple inhibitors, only some of which have differential actions on normal and Ph+/BCR-ABL+ cells.

Download Full-text

Disturbed Secretory Capacity for Macrophage Inflammatory Protein (MIP)-1α and MIP-1β in Progressive HIV Infection

AIDS Research and Human Retroviruses ◽

10.1089/aid.2004.20.1087 ◽

2004 ◽

Vol 20 (10) ◽

pp. 1087-1091 ◽

Cited By ~ 3

Author(s):

Wim Jennes ◽

Chris Vereecken ◽

Katrien Fransen ◽

Ann De Roo ◽

Luc Kestens

Keyword(s):

Hiv Infection ◽

Inflammatory Protein ◽

Macrophage Inflammatory Protein ◽

Secretory Capacity

Download Full-text

Levels of Macrophage Inflammatory Protein 1α (MIP-1α) and MIP-1β in Intervillous Blood Plasma Samples from Women with Placental Malaria and Human Immunodeficiency Virus Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.4.631-636.2003 ◽

2003 ◽

Vol 10 (4) ◽

pp. 631-636 ◽

Cited By ~ 29

Author(s):

Sujittra Chaisavaneeyakorn ◽

Julie M. Moore ◽

Lisa Mirel ◽

Caroline Othoro ◽

Juliana Otieno ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hiv Infection ◽

Blood Plasma ◽

Plasma Levels ◽

Placental Malaria ◽

Hiv Positive ◽

Inflammatory Protein ◽

Immunodeficiency Virus ◽

Macrophage Inflammatory Protein ◽

Hiv Negative

ABSTRACT Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β play an important role in modulating immune responses. To understand their importance in immunity to placental malaria (PM) and in human immunodeficiency virus (HIV)-PM coinfection, we investigated levels of these chemokines in the placental intervillous blood plasma (IVB plasma) and cord blood plasma of HIV-negative PM-negative, HIV-negative PM-positive, HIV-positive PM-negative, and HIV-positive PM-positive women. Compared to HIV-negative PM-negative women, the MIP-1β concentration in IVB plasma was significantly elevated in HIV-negative PM-positive women and HIV-positive PM-positive women, but it was unaltered in HIV-positive PM-negative women. Also, PM-infected women, irrespective of their HIV status, had significantly higher levels of MIP-1β than HIV-positive PM-negative women. The MIP-1α level was not altered in association with either infection. The IVB plasma levels of MIP-1α and MIP-1β positively correlated with the cord blood plasma levels of these chemokines. As with IVB plasma, only cord plasma from PM-infected mothers had significantly elevated levels of MIP-1β compared to PM-negative mothers, irrespective of their HIV infection status. MIP-1β and MIP-1α levels in PM-positive women were positively associated with parasite density and malaria pigment levels. Regardless of HIV serostatus, the IVB MIP-1β level was significantly lower in women with PM-associated anemia. In summary, an elevated level of MIP-1β was associated with PM. HIV infection did not significantly alter these two chemokine levels in IVB plasma.

Download Full-text