PMID- 9670984
OWN - NLM
STAT- MEDLINE
DCOM- 19980730
LR  - 20220129
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 161
IP  - 2
DP  - 1998 Jul 15
TI  - Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of 
      cell polarization in response to monocyte chemoattractant protein-1 and 
      formyl-methionyl-leucyl-phenylalanine.
PG  - 1026-33
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by 
      trombocytopenia, eczema, and progressive decline of the immune function. In 
      addition, lymphocytes and platelets from WAS patients have morphologic 
      abnormalities. Since chemokines may induce morphologic changes and migration of 
      leukocytes, we investigated the monocyte response to chemoattractants in cells 
      from WAS patients with an identified mutation in the WAS protein gene. Here, we 
      report that monocytes derived from four patients with molecularly defined typical 
      WAS have a severely impaired migration in response to FMLP and to the chemokines 
      monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory 
      protein-1alpha compared with normal donors. Conversely, neither MCP-1 binding to 
      monocytes nor induction of the respiratory burst by MCP-1 and FMLP is 
      significantly different between WAS patients and normal donors. Within a few 
      minutes of stimulation, monocytes respond to chemokines with increased expression 
      of adhesion molecules and with morphologic changes such as cell polarization. 
      Although up-regulation of CD11b/CD18 expression following stimulation with FMLP 
      or MCP-1 is preserved in WAS patients, cell polarization is dramatically 
      decreased. Staining of F-actin by FITC-phalloidin in monocytes stimulated with 
      chemoattractants shows F-actin to have a rounded shape in WAS patients, as 
      opposed to the polymorphic distribution of F-actin in the polarized monocytes 
      from healthy donors. These results suggest that WAS protein is involved in the 
      monocyte response to the chemokines MCP-1 and macrophage inflammatory 
      protein-1alpha.
FAU - Badolato, R
AU  - Badolato R
AD  - Clinica Pediatrica, Universita' di Brescia, Italy. badolato@master.cci.unibs.it
FAU - Sozzani, S
AU  - Sozzani S
FAU - Malacarne, F
AU  - Malacarne F
FAU - Bresciani, S
AU  - Bresciani S
FAU - Fiorini, M
AU  - Fiorini M
FAU - Borsatti, A
AU  - Borsatti A
FAU - Albertini, A
AU  - Albertini A
FAU - Mantovani, A
AU  - Mantovani A
FAU - Ugazio, A G
AU  - Ugazio AG
FAU - Notarangelo, L D
AU  - Notarangelo LD
LA  - eng
GR  - E.0635/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
SB  - IM
MH  - Cell Movement/drug effects/immunology
MH  - Cell Polarity/drug effects/*immunology
MH  - Cell Size/drug effects/immunology
MH  - Chemokine CCL2/blood/metabolism/*pharmacology
MH  - Chemotaxis, Leukocyte/drug effects/*immunology
MH  - Child, Preschool
MH  - Humans
MH  - Infant
MH  - Monocytes/*immunology/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Protein Binding/immunology
MH  - Wiskott-Aldrich Syndrome/*immunology
EDAT- 1998/07/22 00:00
MHDA- 1998/07/22 00:01
CRDT- 1998/07/22 00:00
PHST- 1998/07/22 00:00 [pubmed]
PHST- 1998/07/22 00:01 [medline]
PHST- 1998/07/22 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1998 Jul 15;161(2):1026-33.