PubMed · 12620758
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Ken-ichiro Inoue, Hirohisa Takano, Toshikazu Yoshikawa. 2003-03-01. Comments on the common cold.. https://doi.org/10.1016/s0140-6736(03)12638-4
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BACKGROUND: Eosinophil migration in the tissue is one characteristic feature of allergic diseases. The CC chemokine eotaxin plays a pivotal role in local accumulation of eosinophils. Myosin light chain kinase (MLCK) is known to regulate cytoskeletal rearrangement and cell motility by means of phosphorylation of myosin light chain (MLC). OBJECTIVE: We have previously shown that mitogen-activated protein (MAP) kinases are important for eosinophil migration. In the present study we hypothesized that MLCK is downstream of MAP kinases, thereby linking the MAP kinase pathway to the activation of cytoskeletal components required for eosinophil chemotaxis. METHODS: Blood eosinophils were purified by using Percoll and anti-CD16 antibody-coated magnetic beads. We investigated the phosphorylation of MLCK and MLC by using the phosphorous 32-orthophosphates-labeled eosinophils. The kinase activity of MLCK was determined by measuring the phosphotransferase activity for the MLCK-specific peptide substrate. The chemotaxis assay was performed in a 48-well Boyden microchamber. RESULTS: The phosphotransferase activity of MLCK for a substrate peptide was enhanced in eotaxin-stimulated eosinophils. We also found that eotaxin induced phosphorylation of MLCK in vivo in phosphorous 32-orthophosphate-labeled eosinophils. PD98059 (MAP/extracellular signal-regulated kinase inhibitor) or SB202190 (p38 MAP kinase inhibitor) abrogated the eotaxin-induced phosphorylation of MLCK. The phosphorylation of MLC was upregulated by eotaxin. Eosinophil chemotaxis was inhibited by means of pretreatment of the MLCK inhibitor ML-7. CONCLUSION: These results suggest that eotaxin regulates MLCK through both extracellular signal-regulated kinase 1/2 and p38 MAP kinase. MLCK activation is a critical step in the cytoskeletal rearrangements leading to eosinophil migration.
OBJECTIVE: To characterize peripheral eosinophil migration in patients with chronic rhinosinusitis in the presence of nasal mucin and nasal tissue extracts. STUDY DESIGN: Prospective, controlled, ex-vivo. METHODS: Peripheral blood eosinophils, nasal mucin, and nasal tissue were harvested at the time of sinus surgery in 10 patients, as well as obtained in 10 healthy control subjects. Extracts were prepared from nasal mucin and nasal tissue. A modified Boyden chamber was used to study eosinophil migration from both patients and healthy control subjects in the presence of both extracts. RESULTS: Patients with chronic rhinosinusitis and all healthy control subjects demonstrated a concentration-dependent increased migration of eosinophils in the presence of both nasal mucin and nasal tissue extracts. The percentage of migration was consistently higher for eosinophils from patients with chronic rhinosinusitis compared with control subjects. The difference attained statistical significance in the presence of 50% tissue extract (median percentage of migration, 23.3% vs. 7.8% [ P=.033]). CONCLUSIONS: Nasal mucin and nasal tissue in chronic rhinosinusitis contains chemoattractants, which can induce active eosinophil migration. The eosinophil migration from patients with chronic rhinosinusitis was consistently higher compared with eosinophils from healthy control subjects. Because the eosinophils were obtained from the peripheral blood, this finding suggests activation of eosinophils in the systemic circulation in chronic rhinosinusitis.
BACKGROUND: Both CXC and CC chemokines play an important role in leukocyte recruitment. However, a systematic examination of their production by human airway epithelial cells (HAECs) has not been carried out. The objective of this study was to investigate whether Th1- and Th2-type cytokines regulate chemokine production in HAECs. METHODS: HAECs were grown from both nasal and bronchial tissue and subsequently stimulated with either Th1- or Th2-type cytokines. RESULTS: Constitutive mRNA expression for gro-alpha, IL-8 and RANTES was seen in both human nasal and human bronchial epithelial cells. IL-4 was the strongest stimulus for both gene expression and protein production of the chemokines RANTES, IL-8 and gro-alpha, while both IL-13 and IFN-gamma were weaker inducers of these chemokines, with the exception of gro-alpha (IL-13 was a strong stimulus for gro-alpha production). TNF-alpha synergized with IL-4, and to a lesser extent with IFN-gamma and IL-13, to release RANTES, IL-8 and gro-alpha. IL-4 and to a lesser extent IL-13 and IFN-gamma stimulated the production of MCP-3 and -4, eotaxin and eotaxin-2 immunoreactivities. However, no induction of the mRNAs encoding these chemokines was observed, suggesting that they may be released from a preformed pool within the HAECs. CONCLUSION: These findings suggest that when released into the airways, Th2- and to a lesser extent Th1-type cytokines may stimulate recruitment of eosinophils and neutrophils through the release of CC (RANTES, MCP-3 and -4, eotaxin and eotaxin-2) and CXC chemokines (gro-alpha and IL-8).