Biologically active neutrophil chemokine pattern in tonsillitis

Abstract

SUMMARYTo gain an insight into the mechanisms of chronic and acute inflammation, the production of neutrophil chemokines in different types of tonsillitis -hyperplastic tonsillitis (HT), recurrent tonsillitis (RT) and peritonsillar abscesses (PA) -was investigated. The chemokines interleukin-8 (IL-8), growth-related oncogene-a (GRO-a ), epithelial cell-derived neutrophil attractant-78 (ENA-78) and granulocyte chemotactic protein-2 (GCP-2) were detected and shown to have different biological activities. With respect to the biological properties of CXC chemokines, the biological activity of the chemokines was identified using a three-step high-performance liquid chromatography (HPLC) technique, a bioassay involving measurement of neutrophil chemotaxis in a single Boyden chamber in tissue of HT, RT and PA. Using reverse transcription-polymerase chain reaction (RT-PCR), the chemokine concentrations were determined in the different tonsillitis entities. The chemokine pattern was dominated in PA by IL-8 and GRO-a and in RT by GRO-a . Hyperplastic tonsils of patients without a history of infection generated about five times lower IL-8 than PA. A protein concentration of GCP-2 was induced in PA and RT, whereas ENA-78 remained the same in all entities. In conclusion, it would appear that IL-8 was upregulated in acute inflammation, whereas GRO-a dominated in chronic inflammation. ENA-78 seems not to play a pivotal role in inflammatory processes in tonsils. GCP-2 may serve as a substitute chemokine in certain inflammatory conditions as its quantity of mRNA and protein was higher in RT and PA than in HT.

Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2

“…IL-8 and ENA-78 ELR ϩ CXC chemokines recruit neutrophils by binding and activating CXCR-2 receptors, 7 whereas IL-8, but not ENA-78, binds to CXCR-1 receptors. 4,8 Results in the present report indicate that PLD1 is differentially activated by CXCR-1, whereas CXCR-2 (and possibly CXCR-1) mediates PLD2 activation.…”

“…Known major neutrophil chemoattractants are the tripeptide FMLP, the lipids LTB 4 and PAF, the activated complement protein C5a, 1,2 and a group of cytokines collectively known as ELR ϩ CXC chemokines. [3][4][5][6] These chemokines are characterized by the invariable presence of the Cys-X-Cys (CXC) consensus motif in the N-terminus of the protein, which is preceded by the amino acid sequence Glu-Leu-Arg (ELR).…”

“…[3][4][5][6] These chemokines are characterized by the invariable presence of the Cys-X-Cys (CXC) consensus motif in the N-terminus of the protein, which is preceded by the amino acid sequence Glu-Leu-Arg (ELR). Classical neutrophil ELR ϩ CXC chemokines are IL-8 (CXCL8); ENA-78 (CXCL5); GRO␣, GRO␤, and GRI␥; NAP-2; and GCP-2.…”

“…7 Apart from binding to CXCR-2, IL-8 and GCP-2 also bind to another class of receptors, the CXCR-1. 4,8 Neutrophil chemotaxis depends on PI3K␥ and Akt/PKB, 9-11 whereas FMLP fails to induce cell directionality in PI3K␥-deprived neutrophils. 12 Pharmacologic studies, however, do not indicate an absolute requirement for PIP 3 .…”

A Chemokine-Degrading Extracellular Protease Made by Group AStreptococcusAlters Pathogenesis by Enhancing Evasion of the Innate Immune Response

“…To this end we assayed whether SpyCEP cleaved human chemokines GCP-2 and GRO␣ in vitro. These chemokines were chosen for analysis due to their abundant expression by tonsillar surface epithelial cells during tonsillitis, which suggests they participate in inflammation (24,25). In addition, GCP-2 and GRO␣ share similar levels of amino acid identity with IL-8 as MIP-2 (see Fig.…”