TY - JOUR
T1 - RANTES- and interleukin-8-induced responses in normal human eosinophils
T2 - Effects of priming with interleukin-5
AU - Schweizer, René C.
AU - Welmers, Berris A C
AU - Raaijmakers, Jan A M
AU - Zanen, Pieter
AU - Lammers, Jan Willem J
AU - Koenderman, Leo
PY - 1994/6/15
Y1 - 1994/6/15
N2 - We report that responses of normal human eosinophils toward the chemokines RANTES and interleukin-8 (IL-8) are modulated and upregulated by priming with IL-5. In a modified Boyden chamber assay, we studied migratory responses toward the members of the chemokine family RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) (C-C subfamily), and IL-8, platelet factor-4 (PF-4), and neutrophil-activating peptide-2 (NAP-2) (C-x-C subfamily). These chemokines were also studied in terms of actin polymerization and ([Ca2+](i))-mobilizing properties, intracellular signals that are thought to play a role during migratory responses. We found that eosinophils showed significant migratory responses toward RANTES and IL-8 at concentrations of 10-9 to 10-7 mol/L only after priming with IL-5 (10 pmol/L). At these concentrations, PF-4, NAP-2, MCP-1, and MIP-1α induced no significant migratory responses after priming. Unprimed eosinophils only showed a significant migratory response toward RANTES (10-6 mol/L). Changes in [Ca2+](i) were found after addition of RANTES, MIP-1α, and NAP-2 (10 nmol/L) to unprimed eosinophils. RANTES (10- 9 to 10-7 mol/L) significantly induced actin polymerization both in primed and unprimed eosinophils, whereas IL-8 (10-9 to 10-8 mol/L) and MIP-1α (10-8 mol/L) only induced actin polymerization after priming with IL-5. NAP-2, PF-4, and MCP-1 did not affect actin polymerization. These findings are further evidence for the hypothesis that cytokines like IL-5 and locally secreted chemokines like RANTES and IL-8 are both at the basis of specific eosinophil influx into the allergic inflammatory locus.
AB - We report that responses of normal human eosinophils toward the chemokines RANTES and interleukin-8 (IL-8) are modulated and upregulated by priming with IL-5. In a modified Boyden chamber assay, we studied migratory responses toward the members of the chemokine family RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) (C-C subfamily), and IL-8, platelet factor-4 (PF-4), and neutrophil-activating peptide-2 (NAP-2) (C-x-C subfamily). These chemokines were also studied in terms of actin polymerization and ([Ca2+](i))-mobilizing properties, intracellular signals that are thought to play a role during migratory responses. We found that eosinophils showed significant migratory responses toward RANTES and IL-8 at concentrations of 10-9 to 10-7 mol/L only after priming with IL-5 (10 pmol/L). At these concentrations, PF-4, NAP-2, MCP-1, and MIP-1α induced no significant migratory responses after priming. Unprimed eosinophils only showed a significant migratory response toward RANTES (10-6 mol/L). Changes in [Ca2+](i) were found after addition of RANTES, MIP-1α, and NAP-2 (10 nmol/L) to unprimed eosinophils. RANTES (10- 9 to 10-7 mol/L) significantly induced actin polymerization both in primed and unprimed eosinophils, whereas IL-8 (10-9 to 10-8 mol/L) and MIP-1α (10-8 mol/L) only induced actin polymerization after priming with IL-5. NAP-2, PF-4, and MCP-1 did not affect actin polymerization. These findings are further evidence for the hypothesis that cytokines like IL-5 and locally secreted chemokines like RANTES and IL-8 are both at the basis of specific eosinophil influx into the allergic inflammatory locus.
UR - http://www.scopus.com/inward/record.url?scp=0028238761&partnerID=8YFLogxK
M3 - Article
C2 - 7515718
AN - SCOPUS:0028238761
SN - 0006-4971
VL - 83
SP - 3697
EP - 3704
JO - Blood
JF - Blood
IS - 12
ER -