PMID- 10857792
OWN - NLM
STAT- MEDLINE
DCOM- 20000630
LR  - 20061115
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 43
IP  - 6
DP  - 2000 Jun
TI  - Treatment of rolling neutrophils with antineutrophil cytoplasmic antibodies 
      causes conversion to firm integrin-mediated adhesion.
PG  - 1337-45
AB  - OBJECTIVE: The vascular lesions associated with autoimmune small-vessel 
      vasculitis may arise from activation of circulating neutrophils by antineutrophil 
      cytoplasmic antibodies (ANCA), resulting in increased adhesion of these 
      neutrophils to the vessel wall. The present study examined the effects of 
      ANCA-positive IgG (ANCA IgG), derived from patients with small-vessel vasculitis, 
      on neutrophil adhesion. METHODS: An in vitro, flow-based adhesion assay was used 
      to determine the effects of ANCA IgG on neutrophils rolling on P-selectin 
      presented by a monolayer of activated platelets. The platelets act as a surrogate 
      vessel wall and can also support beta2 integrin-mediated immobilization of 
      neutrophils if they are purposefully activated (e.g., by FMLP). RESULTS: In the 
      absence of any added agents, neutrophils rolled continuously over the platelet 
      monolayer. Superfusion of ANCA IgG over rolling cells resulted in conversion to 
      stationary adhesion accompanied by shape change. The ANCA-mediated response was 
      transient, peaking at 5-6 minutes and returning to baseline by 15 minutes, even 
      in the continued presence of ANCA. In contrast, normal (ANCA-negative) IgG and 
      ANCA F(ab')2 fragments caused minimal conversion to stationary adhesion. 
      Pretreatment of neutrophils with blocking antibodies directed toward Fc gamma 
      receptor type IIA or the integrin chain CD11b completely inhibited the 
      ANCA-mediated conversion, confirming that ANCA-mediated activation occurred 
      through Fc gamma receptors and that neutrophil immobilization was mediated by the 
      activated beta2 integrin (CD11b/CD18). CONCLUSION: These findings support the 
      concept that ANCA can directly activate neutrophils to become firmly adherent to 
      vessel walls, where they may obstruct flow, initiate tissue damage, and 
      contribute to pathogenesis of vasculitis.
FAU - Radford, D J
AU  - Radford DJ
AD  - The University of Birmingham, UK.
FAU - Savage, C O
AU  - Savage CO
FAU - Nash, G B
AU  - Nash GB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Antibodies/pharmacology
MH  - Antibodies, Antineutrophil Cytoplasmic/*pharmacology
MH  - Blood Platelets
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/drug effects
MH  - Humans
MH  - Immunoglobulin Fab Fragments/pharmacology
MH  - Immunoglobulin G/pharmacology
MH  - Macrophage-1 Antigen/immunology/*physiology
MH  - Neutrophils/*drug effects/*physiology
MH  - Receptors, IgG/immunology
MH  - Time Factors
EDAT- 2000/06/17 09:00
MHDA- 2000/07/08 11:00
CRDT- 2000/06/17 09:00
PHST- 2000/06/17 09:00 [pubmed]
PHST- 2000/07/08 11:00 [medline]
PHST- 2000/06/17 09:00 [entrez]
AID - 10.1002/1529-0131(200006)43:6<1337::AID-ANR16>3.0.CO;2-M [doi]
PST - ppublish
SO  - Arthritis Rheum. 2000 Jun;43(6):1337-45. doi: 
      10.1002/1529-0131(200006)43:6<1337::AID-ANR16>3.0.CO;2-M.