RANTES- and interleukin-8-induced responses in normal human eosinophils: effects of priming with interleukin-5

Abstract

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.

Elevated levels of eotaxin and interleukin-5 in blister fluid of bullous pemphigoid: correlation with tissue eosinophilia

“…18 Moreover, the chemokine response of normal eosinophils is modulated and upregulated by priming with IL-5. 19 Eosinophil-specific chemokines such as eotaxin recruit eosinophils from blood microvessels, and IL-5 facilitates this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. 11 From these findings we speculate that both eotaxin and IL-5 are indispensable for the lesional infiltration of eosinophils.…”

CC chemokine ligand-2 synergizes with the nonchemokine G protein-coupled receptor ligand fMLP in monocyte chemotaxis, and it cooperates with the TLR ligand LPS via induction of CXCL8

“…Several studies have shown that priming of leukocytes with cytokines enhanced migration to inflammatory chemokines [4,[11][12][13][14][15][16]. In a further attempt to study the direct synergy between chemokines and inflammatory cytokines, IL-1␤ or IFN-␥ was combined with CCL2 in the THP-1 Multiscreen chemotaxis system.…”

“…Priming is a well-described phenomenon in which pre-exposure of leukocytes to TLR ligands or cytokines sensitizes cells to guarantee optimal responses to extracellular inflammatory stimuli, including chemokines [4,[11][12][13][14][15]. For example, when eosinophils were preincubated with the cytokine IL-5, their chemotactic activity toward eotaxin was enhanced [13,16].…”

Pulmonary eosinophilia requires interleukin-5, eotaxin-1, and CD4+ T cells in mice immunized with respiratory syncytial virus G glycoprotein

“…IL-5 plays a role in the proliferation, differentiation, and recruitment of B cells and eosinophils. In addition to roles in eosinophil proliferation, differentiation, and recruitment [18 -21], IL-5 primes eosinophils for recruitment by other cytokines and chemokines, such as IL-8 [22], RANTES [22], and eotaxin-1 [20]. Thus, IL-5 is involved in eosinophil function at multiple stages, including development, chemotaxis, and activation.…”