PMID- 8133057
OWN - NLM
STAT- MEDLINE
DCOM- 19940419
LR  - 20161123
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 152
IP  - 5
DP  - 1994 Mar 1
TI  - Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, 
      TGF-beta 3) is mediated by fibronectin.
PG  - 2456-66
AB  - TGF-beta isoforms regulate numerous cellular functions including cell growth and 
      differentiation, the cellular synthesis and secretion of extracellular matrix 
      proteins, such as fibronectin (Fn), and the immune response. We have previously 
      shown that TGF-beta 1 is the most potent chemoattractant described for human 
      peripheral blood neutrophils (PMNs), suggesting that TGF-beta s may play a role 
      in the recruitment of PMNs during the initial phase of the inflammatory response. 
      In our current studies, we demonstrate that the maximal chemotactic response was 
      attained near 40 fM for all mammalian TGF-beta isoforms. However, there was a 
      statistically significant difference in migratory distance of the PMNs: TGF-beta 
      2 (556 microM) > TGF-beta 3 (463 microM) > TGF-beta 1 (380 microM) (beta 2: beta 
      3, p < or = 0.010; beta 3: beta 1, p < or = 0.04; beta 2: beta 1, p < or = 
      0.0012). A mAb to the cell binding domain (CBD) of Fn inhibited the chemotactic 
      response to TGF-beta 1 and TGF-beta 3 by 63% and to TGF-beta 2 by 70%, whereas 
      the response to FMLP, a classic chemoattractant, was only inhibited by 18%. In 
      contrast, a mAb to a C-terminal epitope of Fn did not retard migration (< 1.5%). 
      The Arg-gly-Asp-ser tetrapeptide inhibited chemotaxis by approximately the same 
      extent as the anti-CBD (52 to 83%). Furthermore, a mAb against the VLA-5 integrin 
      (VLA-5; Fn receptor) also inhibited TGF-beta-induced chemotaxis. These results 
      indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by 
      the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin 
      on the PMN cell surface, primarily the VLA-5 integrin. TGF-beta isoforms also 
      elicited the release of cellular Fn from PMNs; we observed a 2.3-fold increase in 
      Fn (389 to 401 ng/ml) in the supernatants of TGF-beta-stimulated PMNs compared 
      with unstimulated cells (173.6 ng/ml). The concentration of TGF-beta required to 
      cause maximal release of Fn from PMNs (4000 fM) is a concentration at which 
      TGF-beta is no longer chemotactic, suggesting that PMNs only use Fn that is 
      constitutively expressed for migration. At higher concentrations of TGF-beta, the 
      Fn released may accumulate basal to the cell, ultimately retarding cellular 
      migration and modulating the chemotactic response.
FAU - Parekh, T
AU  - Parekh T
AD  - Department of Pathology, New York University Medical School, NY 10016.
FAU - Saxena, B
AU  - Saxena B
FAU - Reibman, J
AU  - Reibman J
FAU - Cronstein, B N
AU  - Cronstein BN
FAU - Gold, L I
AU  - Gold LI
LA  - eng
GR  - AR11949-27/AR/NIAMS NIH HHS/United States
GR  - CA 16807/CA/NCI NIH HHS/United States
GR  - CA 49507/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Comparative Study
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 (Antibodies, Monoclonal)
RN  - 0 (Fibronectins)
RN  - 0 (Integrins)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Fibronectin)
RN  - 0 (Transforming Growth Factor beta)
RN  - AC6UDA2MFC (arginyl-glycyl-aspartyl-serine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antibodies, Monoclonal
MH  - Chemotaxis, Leukocyte/*drug effects/physiology
MH  - Fibronectins/antagonists & inhibitors/genetics/*physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Integrins/physiology
MH  - Molecular Sequence Data
MH  - Neutrophils/*drug effects/immunology/*physiology
MH  - Oligopeptides/chemistry/pharmacology
MH  - Receptors, Fibronectin/antagonists & inhibitors/physiology
MH  - Transforming Growth Factor beta/classification/*pharmacology
EDAT- 1994/03/01 00:00
MHDA- 1994/03/01 00:01
CRDT- 1994/03/01 00:00
PHST- 1994/03/01 00:00 [pubmed]
PHST- 1994/03/01 00:01 [medline]
PHST- 1994/03/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1994 Mar 1;152(5):2456-66.