PMID- 10648122
OWN - NLM
STAT- MEDLINE
DCOM- 20000328
LR  - 20171116
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 198
IP  - 2
DP  - 1999 Dec 15
TI  - CD154 (CD40L) induces human endothelial cell chemokine production and migration 
      of leukocyte subsets.
PG  - 87-95
AB  - CD154-CD40 interactions play key roles in humoral and cellular immune responses. 
      With regard to the latter, ligation of CD40 on endothelial cells upregulates 
      important intercellular adhesion molecules. Activated endothelial cells also 
      regulate leukocyte trafficking into inflammatory sites by secreting chemokines. 
      In this study we asked whether CD154 mediated signals induce human umbilical vein 
      endothelial cells (HUVEC) to secrete neutrophil or peripheral blood mononuclear 
      cell (PBMC) chemoattractants. HUVEC were cocultured with CD154(+) Jurkat D1.1 
      cells in the presence or in the absence of anti-CD154 mAb or control mAb. 
      Additionally, HUVEC were cocultured with control CD154(-) Jurkat B2.7 cells. 
      Supernatants were harvested after 24 h and chemotaxis assays performed. 
      Supernatants derived from Jurkat cells did not induce either neutrophil or PBMC 
      chemotaxis. Resting endothelial cells produce at baseline some neutrophil and 
      PBMC chemoattractants. However, there was significantly enhanced neutrophil and 
      PBMC chemoattractant activity in supernatants derived from CD154 stimulated 
      HUVEC. The enhanced leukocyte migration was specifically inhibited by anti-CD154 
      mAb. Anti-chemokine mAbs were used to identify specific chemokines mediating the 
      enhanced leukocyte chemotaxis activity in CD154 stimulated HUVEC supernatants. 
      There was complete or near complete inhibition of enhanced neutrophil and PBMC 
      migration by anti-IL-8 and anti-monocyte chemoattractant protein-1 (MCP-1) mAbs, 
      respectively. Anti-RANTES mAb partially blocked the enhanced PBMC migration, 
      whereas anti-macrophage inflammatory protein-1alpha (MIP-1alpha) mAb had no 
      effect. Utilizing specific ELISAs, we confirmed that CD40 ligation induces HUVEC 
      to secrete IL-8, MCP-1, and RANTES, but not MIP-1alpha. Finally, we present 
      evidence that the effects of CD154-CD40 interactions on HUVEC chemokine 
      production are independent of IL-1beta production. These findings demonstrate 
      that CD154-CD40 interactions induce endothelial cells to produce specific 
      neutrophil and mononuclear cell chemoattractants.
CI  - Copyright 1999 Academic Press.
FAU - Thienel, U
AU  - Thienel U
AD  - Department of Medicine, Columbia University, New York, New York 10032, USA.
FAU - Loike, J
AU  - Loike J
FAU - Yellin, M J
AU  - Yellin MJ
LA  - eng
GR  - R01 AR44198/AR/NIAMS NIH HHS/United States
GR  - R01 HL52145/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (Membrane Glycoproteins)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - CD40 Antigens/physiology
MH  - CD40 Ligand
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokine CCL5/biosynthesis
MH  - Chemokines/*biosynthesis
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Endothelium, Vascular/*metabolism
MH  - Humans
MH  - Interleukin-1/physiology
MH  - Interleukin-8/biosynthesis
MH  - Membrane Glycoproteins/*pharmacology
MH  - Neutrophils/*immunology
EDAT- 2000/01/29 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/01/29 09:00 [entrez]
AID - S0008-8749(99)91583-6 [pii]
AID - 10.1006/cimm.1999.1583 [doi]
PST - ppublish
SO  - Cell Immunol. 1999 Dec 15;198(2):87-95. doi: 10.1006/cimm.1999.1583.