Synergism between interleukin-8 and tumor necrosis factor-alpha for neutrophil-mediated platelet activation.
We previously showed that two polymorphonuclear neutrophil (PMN)-derived proteinases, namely cathepsin G (Cat. G) and elastase (HLE), acting in synergy activated nearby platelets in vitro. This cellular interaction could result in a pathology such as the adult respiratory distress syndrome (ARDS). Since elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were detected in these patients and therefore could be involved in this disease, we looked for their effects in the PMN-platelet cooperation system. Addition of IL-8 to mixed suspensions of PMN and platelets induced weak but significant platelet aggregations. Upon preincubation with TNF-alpha, aggregations triggered by IL-8 were significantly increased. The targets of these cytokines were not the platelets but the PMNs. This was shown by following beta-glucuronidase release and more interestingly by measuring the enzymatic activities of Cat. G and HLE in the supernatant. Inhibition of the platelet response upon addition of a serine proteinase inhibitor, eglin C, clearly demonstrated the involvement of these two enzymes. Taken together, these results constitute an additional argument for the role of the PMN-platelet interaction in ARDS.
Si Tahar
M
M
Unité de Pharmacologie Cellulaire, Institut Pasteur, Paris, France.
Renesto
P
P
Balloy
V
V
Chignard
M
M
D000328:Adult; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000008:administration & dosage* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011506:Proteins; D012128:Respiratory Distress Syndrome / Q000209:etiology; D012697:Serine Endopeptidases; D015843:Serpins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000502:physiology
D016209:Interleukin-8; D011506:Proteins; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; C028656:eglin proteinase inhibitors; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase