PMID- 10072545
OWN - NLM
STAT- MEDLINE
DCOM- 19990414
LR  - 20131121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 5
DP  - 1999 Mar 1
TI  - Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 
      pathways.
PG  - 2946-55
AB  - To investigate eosinophil stimulation by chemokines we developed a sensitive 
      assay of leukocyte shape change, the gated autofluorescence/forward scatter 
      assay. Leukocyte shape change responses are mediated through rearrangements of 
      the cellular cytoskeleton in a dynamic process typically resulting in a polarized 
      cell and are essential to the processes of leukocyte migration from the 
      microcirculation into sites of inflammation. We examined the actions of the 
      chemokines eotaxin, eotaxin-2, monocyte chemoattractant protein-1 (MCP-1), MCP-3, 
      MCP-4, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and IL-8 on 
      leukocytes in mixed cell suspensions and focused on the responses of eosinophils 
      to C-C chemokines. Those chemokines acting on CCR3 induced a rapid shape change 
      in eosinophils from all donors; of these, eotaxin and eotaxin-2 were the most 
      potent. Responses to MCP-4 were qualitatively different, showing marked reversal 
      of shape change responses with agonist concentration and duration of treatment. 
      In contrast, MIP-1alpha induced a potent response in eosinophils from a small and 
      previously undescribed subgroup of donors via a non-CCR3 pathway likely to be 
      CCR1 mediated. Incubation of leukocytes at 37 degrees C for 90 min in the absence 
      of extracellular calcium up-regulated responses to MCP-4 and MIP-1alpha in the 
      majority of donors, and there was a small increase in responses to eotaxin. 
      MIP-1alpha responsiveness in vivo may therefore be a function of both CCR1 
      expression levels and the regulated efficiency of coupling to intracellular 
      signaling pathways. The observed up-regulation of MIP-1alpha signaling via 
      non-CCR3 pathways may play a role in eosinophil recruitment in inflammatory 
      states such as occurs in the asthmatic lung.
FAU - Sabroe, I
AU  - Sabroe I
AD  - Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School 
      of Medicine, South Kensington, London, United Kingdom.
FAU - Hartnell, A
AU  - Hartnell A
FAU - Jopling, L A
AU  - Jopling LA
FAU - Bel, S
AU  - Bel S
FAU - Ponath, P D
AU  - Ponath PD
FAU - Pease, J E
AU  - Pease JE
FAU - Collins, P D
AU  - Collins PD
FAU - Williams, T J
AU  - Williams TJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CCL11 protein, human)
RN  - 0 (CCL13 protein, human)
RN  - 0 (CCR1 protein, human)
RN  - 0 (CCR3 protein, human)
RN  - 0 (Chemokine CCL11)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CC)
RN  - 0 (Cytokines)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, CCR3)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Virulence Factors, Bordetella)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Chemokine CCL11
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Chemokines/*pharmacology
MH  - *Chemokines, CC
MH  - Cytokines/pharmacology
MH  - Eosinophils/*drug effects/physiology
MH  - Flow Cytometry
MH  - Humans
MH  - Macrophage Inflammatory Proteins/pharmacology
MH  - Monocyte Chemoattractant Proteins/pharmacology
MH  - Monocytes/physiology
MH  - Neutrophils/drug effects/physiology
MH  - Receptors, CCR1
MH  - Receptors, CCR3
MH  - Receptors, Chemokine/*physiology
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Mar 1;162(5):2946-55.