PMID- 12885942
OWN - NLM
STAT- MEDLINE
DCOM- 20030909
LR  - 20211203
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 74
IP  - 2
DP  - 2003 Aug
TI  - Chemokine receptor expression and chemotactic responsiveness of human monocytes 
      after influenza A virus infection.
PG  - 252-9
AB  - Chemokines and their receptors play an important role in site-directed migration 
      and activation of leukocytes. To understand how viral infections may impair this 
      function, we analyzed chemokine receptor expression and responsiveness of human 
      monocytes after infection with influenza A virus. Whereas treatment with 
      infectious virus induced a rapid down-regulation of the CCL2/monocyte 
      chemoattractant protein-1 (MCP-1)-specific receptor CCR2, inactivated virus did 
      not significantly alter CCR2 surface expression. In parallel, the response to 
      CCL2/MCP-1 was lost after infection with active virus: Neither a 
      CCL2/MCP-1-induced shift of intracellular calcium concentrations nor the 
      chemotactic response to CCL2/MCP-1 was detectable. In striking contrast, the 
      presence of CCR1 and CCR5 on the cell surface remained unchanged or was even 
      slightly up-regulated after viral infection. However, the remaining expression of 
      CCR1 and CCR5 correlated reciprocally with an ongoing unresponsiveness to the 
      CCR1 and CCR5 agonists CCL3/macrophage-inflammatory protein-1alpha (MIP-1alpha), 
      CCL4/MIP-1beta, and CCL5/regulated on activation, normal T expressed and secreted 
      (RANTES), all chemokines binding to these two receptors. The 
      CCL3/MIP-1alpha-induced shifts of intracellular calcium concentrations declined 
      gradually to almost undetectable levels, and most conspiciuously, the chemotactic 
      response to CCL3/MIP-1alpha, CCL4/MIP-1beta, and CCL5/RANTES was lost after 
      infection with active influenza virus. Inactivated virus particles did not 
      significantly alter the responsiveness induced by CCR1 and CCR5 agonists. Despite 
      the inability of chemokine receptors to elicit migration, phosphorylation of 
      protein kinase B was not altered in virus-infected monocytes. Thus, influenza A 
      virus infection rapidly abolishes the functional responsiveness of monocytes and 
      prevents an adequate response of the infected cells to chemokine stimulation.
FAU - Salentin, Robert
AU  - Salentin R
AD  - Institute of Immunology, Philipps University, Marburg, Germany. 
      kaufmana@mailer.uni-marburg.de
FAU - Gemsa, Diethard
AU  - Gemsa D
FAU - Sprenger, Hans
AU  - Sprenger H
FAU - Kaufmann, Andreas
AU  - Kaufmann A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (CCR1 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Chemotaxis, Leukocyte/*physiology
MH  - DNA Primers
MH  - Down-Regulation
MH  - Humans
MH  - Influenza A virus/*physiology
MH  - Monocytes/*physiology/virology
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR1
MH  - Receptors, CCR2
MH  - Receptors, CCR5/*metabolism
MH  - Receptors, Chemokine/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/07/30 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/07/30 05:00
PHST- 2003/07/30 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/07/30 05:00 [entrez]
AID - 10.1189/jlb.1102565 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Aug;74(2):252-9. doi: 10.1189/jlb.1102565.