IL-1 beta primes IL-8-activated human neutrophils for elastase release, phospholipase D activity, and calcium flux.
Interleukin-8 (IL-8), the prototype of the alpha (e.i., C-X-C branch) chemokine family, induced elastase release in a concentration-dependent manner (50-1000 ng/mL) in cytochalasin B-treated human polymorphonuclear leukocytes (PMNs). This response was potentiated about twofold if PMNs were preexposed to interleukin-1 beta (IL-1 beta) at concentrations that were by themselves inactive. The effect of IL-1 beta was clearly observed after 5 min and was maximal after a 30-min preincubation of the cells. The effect was present over the whole active concentration range of IL-8 and was completely blocked by the presence of IL-1 receptor antagonist. Priming of elastase release by IL-1 beta was not associated with a change in receptor number or affinity for IL-8. On the contrary, it was correlated with priming of phospholipase D activity and calcium flux activated by IL-8. Preincubation of the cells with ethanol and/or La3+ inhibited IL-8-induced degranulations, suggesting that activation of phospholipase D and increase of [Ca2+]i were important for this response. In contrast, ethanol and La3+ did not decrease the priming effect of IL-1 beta. IL-8 and IL-1 beta have been shown to be released by the same cell types and may be concomitantly present at sites of inflammation, giving rise to an amplification of the inflammatory response.
Brandolini
L
L
Dompé S.p.A. Research Center, L'Aquila, Italy.
Bertini
R
R
Bizzarri
C
C
Sergi
R
R
Caselli
G
G
Zhou
D
D
Locati
M
M
Sozzani
S
S
D002118:Calcium / Q000097:blood* / Q000378:metabolism*; D015550:Cell Degranulation; D002478:Cells, Cultured; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology*; D019272:Leukocyte Elastase / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D015290:Second Messenger Systems; D012795:Sialoglycoproteins / Q000494:pharmacology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D010712:Phosphatidic Acids; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D000431:Ethanol; D010739:Phospholipase D; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D002118:Calcium