MilliporeSigma
  • Home
  • Search Results
  • Malarial pigment hemozoin impairs chemotactic motility and transendothelial migration of monocytes via 4-hydroxynonenal.

Malarial pigment hemozoin impairs chemotactic motility and transendothelial migration of monocytes via 4-hydroxynonenal.

Free radical biology & medicine (2014-07-16)
Oleksii A Skorokhod, Valentina Barrera, Regine Heller, Franco Carta, Franco Turrini, Paolo Arese, Evelin Schwarzer
ABSTRACT

Natural hemozoin, nHZ, is avidly phagocytosed in vivo and in vitro by human monocytes. The persistence of the undigested β-hematin core of nHZ in the phagocyte lysosome for long periods of time modifies several cellular immune functions. Here we show that nHZ phagocytosis by human primary monocytes severely impaired their chemotactic motility toward MCP-1, TNF, and FMLP, by approximately 80% each, and their diapedesis across a confluent human umbilical vein endothelial cell layer toward MCP-1 by 45±5%. No inhibition was observed with latex-fed or unfed monocytes. Microscopic inspection revealed polarization defects in nHZ-fed monocytes due to irregular actin polymerization. Phagocytosed nHZ catalyzes the peroxidation of polyunsaturated fatty acids and generation of the highly reactive derivative 4-hydroxynonenal (4-HNE). Similar to nHZ phagocytosis, the exposure of monocytes to in vivo-compatible 4-HNE concentrations inhibited cell motility in both the presence and the absence of chemotactic stimuli, suggesting severe impairment of cytoskeleton dynamics. Consequently, 4-HNE conjugates with the cytoskeleton proteins β-actin and coronin-1A were immunochemically identified in nHZ-fed monocytes and mass spectrometrically localized in domains of protein-protein interactions involved in cytoskeleton reorganization and cell motility. The molecular and functional modifications of actin and coronin by nHZ/4-HNE may also explain impaired phagocytosis, another motility-dependent process previously described in nHZ-fed monocytes. Further studies will show whether impaired monocyte motility may contribute to the immunodepression and the frequent occurrence of secondary infections observed in malaria patients.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-Mannitol, tested according to Ph. Eur.
Sigma-Aldrich
D-Mannitol, suitable for plant cell culture
Sigma-Aldrich
D-Mannitol, meets EP, FCC, USP testing specifications
Sigma-Aldrich
D-Mannitol, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
D-Mannitol, ACS reagent
Millipore
D-Mannitol, ACS reagent, suitable for microbiology, ≥99.0%
Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Sigma-Aldrich
Anti-HLA-E antibody produced in mouse, IgG fraction of antiserum, buffered aqueous solution
Supelco
Mannitol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Anti-CD14 antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
Supelco
D-Mannitol, ≥99.9999% (metals basis), for boron determination
Sigma-Aldrich
Anti-CD14 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CD14 antibody produced in rabbit, Ab3, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
USP
Mannitol, United States Pharmacopeia (USP) Reference Standard
Mannitol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, clone UCHM-1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1637, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL1638, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-HLA-E antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, clone MEM-18, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-HLA-E antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-HLA-E antibody produced in mouse, clone MEM-E/08, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, clone B-A8, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-HLA-E antibody produced in mouse, clone MEM-E/06, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-HLA-E antibody produced in mouse, clone MEM-E/07, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-CD14 antibody produced in mouse, clone MEM-15, purified immunoglobulin, buffered aqueous solution