RANTES- and interleukin-8-induced responses in normal human eosinophils: effects of priming with interleukin-5.
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-1 alpha (MIP-1 alpha) (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-1 alpha 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-1 alpha, 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-1 alpha (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.
Schweizer
R C
RC
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Welmers
B A
BA
Raaijmakers
J A
JA
Zanen
P
P
Lammers
J W
JW
Koenderman
L
L
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018946:Chemokine CCL5; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*
D000199:Actins; D018946:Chemokine CCL5; D015848:Interleukin-5; D016209:Interleukin-8; D008222:Lymphokines; D002118:Calcium