PMID- 8534491
OWN - NLM
STAT- MEDLINE
DCOM- 19960208
LR  - 20171116
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 14
IP  - 1
DP  - 1996 Jan
TI  - Effects of integrin clustering on human lung mast cells and basophils.
PG  - 95-103
AB  - The interaction of cells with the extracellular matrix can alter cell responses 
      and is regulated by integrins on the cell surface. We used monoclonal antibodies 
      to the VLA-4 integrins CD29 and CD49d followed by an F(ab')2 fragment of rabbit 
      anti-mouse immunoglobulin G1 to crosslink integrins on the surface of human lung 
      mast cells and basophils. Crosslinking either CD29 or CD49d caused a significant 
      histamine release (HR) from the basophils of most asthmatic donors (10 of 14 for 
      CD49d and 7 of 10 for CD29) (HR = 21 +/- 5%, n = 10, P < 0.005 for CD29 and HR = 
      19 +/- 4%, n = 14, P < 0.01 for CD49d) yet failed to initiate HR from the 
      basophils of non-atopic and atopic donors (HR was 1 +/- 0.5% for CD29 and 1 +/- 
      0.5% for CD49d, n = 10, P = NS). Crosslinking either CD29 or CD49d also failed to 
      initiate histamine release from human lung mast cells (HR was 1 +/- 1% for CD29 
      and 2 +/- 1% for CD49d). The basophils of asthmatic donors responded to 100 and 
      30 micrograms/ml tissue fibronectin (HR = 12 +/- 2% and 10 +/- 3% for 100 and 30 
      micrograms/ml fibronectin, respectively, n = 18, P < 0.05), whereas basophils of 
      nonasthmatic patients again failed to degranulate (HR was 0 +/- 0.4% and 1 +/- 
      0.6%, respectively, n = 11, P = NS). In contrast to the basophil, crosslinking of 
      either CD29 or CD49d failed to initiate histamine release in human lung mast 
      cells (HR = 1 +/- 1% for CD29 and 2 +/- 1%, n = 15). Human lung mast cells were 
      also unresponsive to tissue fibronectin (100 and 30 micrograms/ml) (HR = 1 +/- 
      1%, n = 5). The tyrosine kinase inhibitor, genistein, significantly reduced CD29- 
      and CD49d-induced HR (inhibition = 83 +/- 7% for CD29 and 77 +/- 6% for CD49d, n 
      > or = 5, P < 0.05). A second tyrosine kinase inhibitor, piceatannol, also 
      significantly reduced both CD29- and CD49d-induced HR (inhibition was 62 +/- 19% 
      for CD29 and 56 +/- 14% for CD49d, n = 7, P < or = 0.05). Integrin crosslinking 
      also affected the response to a second, immunoglobulin E (IgE)-dependent 
      stimulus. Both CD29 and CD49d clustering significantly inhibited anti-IgE-induced 
      histamine release from the human basophil. Inhibition was 30 +/- 5%, n = 18, P < 
      or = 0.001 for CD29 versus 40 +/- 6% for CD49d. In summary, we have shown that 
      crosslinking the beta 1 integrins using either monoclonal antibodies or tissue 
      fibronectin can initiate mediator release from the basophils of asthmatic 
      patients by a mechanism which appears to be tyrosine kinase-mediated. In 
      addition, clustering of integrins modulates the response to a second 
      IgE-dependent signal.
FAU - Lavens, S E
AU  - Lavens SE
AD  - Dept. of Physiology and Pharmacology, University of Southampton, Bassett Crescent 
      East, United Kingdom.
FAU - Goldring, K
AU  - Goldring K
FAU - Thomas, L H
AU  - Thomas LH
FAU - Warner, J A
AU  - Warner JA
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fibronectins)
RN  - 0 (Integrin beta1)
RN  - 0 (Integrins)
RN  - 0 (Isoflavones)
RN  - 0 (Stilbenes)
RN  - 143198-26-9 (Integrin alpha4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Antigens, CD/chemistry/immunology/physiology
MH  - Basophils/*physiology
MH  - Cell Degranulation/drug effects
MH  - Cross-Linking Reagents
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibronectins/pharmacology
MH  - Genistein
MH  - Histamine Release/drug effects
MH  - Humans
MH  - Immunoglobulin E/pharmacology
MH  - Integrin alpha4
MH  - Integrin beta1/chemistry/immunology/physiology
MH  - Integrins/*chemistry/*physiology
MH  - Isoflavones/pharmacology
MH  - Lung/*cytology
MH  - Mast Cells/*physiology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Stilbenes/pharmacology
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 10.1165/ajrcmb.14.1.8534491 [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 1996 Jan;14(1):95-103. doi: 
      10.1165/ajrcmb.14.1.8534491.