Effects of extracellular pH on tumour necrosis factor-α production by resident alveolar macrophages

2001 ◽  
Vol 101 (3) ◽  
pp. 267 ◽  
Author(s):  
Thomas A. HEMING ◽  
Sanat K. DAVÉ ◽  
Divina M. TUAZON ◽  
Ashok K. CHOPRA ◽  
Johnny W. PETERSON ◽  
...  
2001 ◽  
Vol 100 (3) ◽  
pp. 259 ◽  
Author(s):  
Thomas A. HEMING ◽  
Divina M. TUAZON ◽  
Sanat K. DAVÉ ◽  
Ashok K. CHOPRA ◽  
Johnny W. PETERSON ◽  
...  

2001 ◽  
Vol 100 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Thomas A. HEMING ◽  
Divina M. TUAZON ◽  
Sanat K. DAVÉ ◽  
Ashok K. CHOPRA ◽  
Johnny W. PETERSON ◽  
...  

The present studies determined the effects of extracellular pH (pHo) on the production of tumour necrosis factor-α (TNF-α) in the macrophage-like cell lines RAW 246.7 and J774 A.1. The cells were activated with lipopolysaccharide (LPS) at pHo 5.5, 6.5 or 7.4. TNF-α gene transcription was monitored by Northern blot analysis. Synthesis of the cytokine was monitored by ELISA measurements of the TNF-α content of cell-conditioned media (extracellularly released TNF-α) and cell lysates (cytosolic TNF-α). The magnitude of the TNF-α response differed markedly between the two cell lines. RAW cells were more responsive to LPS than were J774 cells. However, the effects of pHo on TNF-α production were similar in the two cell lines. TNF-α gene transcription was insensitive to experimental pHo. The pHo had no effect on the abundance of TNF-α mRNA at 2, 4 or 18 h. Nonetheless, synthesis of TNF-α was affected significantly by pHo. The TNF-α contents of cell-conditioned medium and cell lysate at 18 h were reduced progressively at lower pHo values. The data indicate that pHo alters TNF-α production in RAW and J774 cells at a post-transcriptional level. These findings suggest that pHo influences the phenotypic responses of macrophages to activating stimuli and modifies the role that macrophages play in inflammatory and immune actions.


2001 ◽  
Vol 101 (3) ◽  
pp. 267-274 ◽  
Author(s):  
Thomas A. HEMING ◽  
Sanat K. DAVÉ ◽  
Divina M. TUAZON ◽  
Ashok K. CHOPRA ◽  
Johnny W. PETERSON ◽  
...  

Cellular acid–base status has been found to exert selective actions on the effector functions of activated macrophages (mϕ). We examined the effects of extracellular pH (pHo) on the production of tumour necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in resident alveolar mϕ. Cells were obtained by bronchoalveolar lavage of rabbits, activated in vitro with LPS, and cultured at pHo 5.5, 6.5 or 7.4 for up to 18 h. The relative abundance of TNF-α mRNA peaked at ~ 2 h. The peak transcript abundance was increased at lower pHo values. This finding probably reflected pre-transcription/transcription effects of pH, in as much as the stability of TNF-α mRNA induced with phorbol ester was unaffected by the experimental pHo values. TNF-α secretion by LPS-treated mϕ decreased at lower pHo values. The TNF-α content of mϕ-conditioned media decreased progressively with decrements in pHo. The reduced TNF-α secretion at pHo 5.5 was accompanied by an increase in the cytosolic TNF-α content (compared with that at pHo 7.4), indicating that pHo altered TNF-α secretion due, in part, to the intracellular retention of synthesized cytokine (i.e. a post-translation effect). The data show that pHo has multiple effects (pre-transcription/transcription and post-translation) on TNF-α production induced by LPS in resident alveolar mϕ. These results suggest that the role of alveolar mϕ in inflammatory responses is modulated by pHo, which may be important in tumours/abscesses and sites of infection where the external milieu is acidic.


1997 ◽  
Vol 91 (1) ◽  
pp. 31-39 ◽  
Author(s):  
J.L. Tavares ◽  
A. Wangoo ◽  
P. Dilworth ◽  
B. Marshall ◽  
S. Kotecha ◽  
...  

2003 ◽  
Vol 21 (3) ◽  
pp. 421-428 ◽  
Author(s):  
H. Fehrenbach ◽  
G. Zissel ◽  
T. Goldmann ◽  
T. Tschernig ◽  
E. Vollmer ◽  
...  

1993 ◽  
Vol 2 (2) ◽  
pp. 119-122 ◽  
Author(s):  
G. P. Pessina ◽  
L. Paulesu ◽  
F. Corradeschi ◽  
E. Luzzi ◽  
A. Di Stefano ◽  
...  

Some biological parameters before and after an acute episode of cigarette smoking in rats have been evaluated. The carboxyhaemoglobin levels depended either on the number of cigarettes, or on the time of exposure to cigarette smoke and returned to pre-smoking values in about 2 h. The evaluation of the kinetics of alveolar and peritoneal macrophages in rats after a smoking session of three cigarettes within an hour, indicated that alveolar macrophages in the bronchoalveolar lavage fluid significantly increased 8 h after the smoking, whereas the number of peritoneal macrophages remained practically constant. The incubation of these cells for various times at 37°C in a humidified atmosphere, resulted in a spontaneous release, 24 h thereafter, of variable amounts of tumour necrosis factor α (TNFα), which remained practically constant during the following days. Neither alveolar macrophages of control rats, nor peritoneal macrophages of both control and smoking rats were able to release TNFα. Moreover, after lipopolysaccharide induction of alveolar macrophages of both control and smoking rats, an increased release of TNFα was observed, indicating that these cells were in an active state.


1997 ◽  
Vol 10 (8) ◽  
pp. 1767-1773 ◽  
Author(s):  
I. Azevedo ◽  
J. de Blic ◽  
C. H. Dumarey ◽  
P. Scheinmann ◽  
B. B. Vargaftig ◽  
...  

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.


Sign in / Sign up

Export Citation Format

Share Document