Journal ArticleDOI
CXC chemokines and their receptors are expressed in type II cells and upregulated following lung injury.
Jeff N. Vanderbilt,Edward M. Mager,Lennell Allen,Teiji Sawa,Jeanine P. Wiener-Kronish,Robert F. Gonzalez,Leland G. Dobbs +6 more
TLDR
It is shown that freshly isolated alveolar Type II (TII) cells express three of the major proinflammatory CXC chemokines (GRO, CINC-2alpha, and MIP-2) and their cognate receptor CXCR2 and this support a central role for the TII cell as an immunologic effector cell in the alveolus.Abstract:
The proinflammatory CXC chemokines GRO, CINC-2, and macrophage inflammatory protein (MIP)-2 are a closely related family of neutrophil chemoattractants. Here, we report that freshly isolated alveolar Type II (TII) cells express these chemokine mRNAs at much higher levels than do freshly isolated Type I cells or alveolar macrophages (AM). TII cells also express CXCR2, the receptor for these chemokines. Lung injury caused by acid or Pseudomonas aeruginosa (Pa) caused an increase in TII cell expression of chemokine mRNAs and GRO protein. We compared the time courses of chemokine mRNA expression in cultured TII cells and AM. In TII cells, GRO mRNA levels were stable over 4 h, but decreased to undetectable levels by 24 h. CINC2 and MIP-2 mRNA levels were low in freshly isolated cells, increased over 2–4 h in culture, and by 24 h dropped to undetectable levels. In contrast, none of these chemokine mRNAs were detected in freshly isolated AM, but expression was induced by tissue culture. In summary, we have shown that TII alveolar epithelial cells produce three of the major proinflammatory CXC chemokines (GRO, CINC-2, and MIP-2) and their cognate receptor CXCR2. Chemokine expression is upregulated in response to lung injury. These observations support a central role for the TII cell as an immunologic effector cell in the alveolus and raise intriguing questions about how CXC chemokines and receptors modulate diverse normal and pathologic cellular responses in the alveoli. In addition to its primary function in respiration, the lung has developed an efficient host defense network that requires regulated recruitment of inflammatory cells to sites of infection and injury. The primary mediators of inflammatory cell recruitment are the chemokines, small (10 kD), chemotactic cytokines that induce directional migration and activation of leukocytes (reviewed in Ref. 1). There are more than 50 distinct chemokines, broadly classified into C, CC, CXC, and CX3C subgroups based on the arrangement of conserved cysteines located near the amino terminus of the protein. For example, in the CC family of chemokines,read more
Citations
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Biology of alveolar type II cells.
TL;DR: The purpose of this review is to highlight the many metabolic properties of alveolar type II cells, their production of surfactant, their role in innate immunity, and their importance in the repair process after lung injury.
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Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung
Jörg Reutershan,Margaret A. Morris,Tracy L. Burcin,David F. Smith,Daniel Chang,Mary S. Saprito,Klaus Ley +6 more
TL;DR: The data revealed what is believed to be a previously unrecognized role of endothelial and epithelial CXCR2 in LPS-induced PMN recruitment and lung injury.
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Chemokines in acute respiratory distress syndrome.
TL;DR: Recent evidence shows that activated leukocytes and chemokines play a key role in the pathogenesis of ARDS and the expanding number of antagonists of chemokine receptors for inflammatory disorders may hold promise for new medicines to combat ARDS.
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CXCR2 antagonists for the treatment of pulmonary disease.
TL;DR: Clinical trials evaluating small molecule CXCR2 antagonists in COPD, asthma and cystic fibrosis are currently underway and hold considerable promise for identifying novel and efficacious treatments of pulmonary disorders.
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Regulation of surfactant secretion in alveolar type II cells.
TL;DR: Signal transduction pathways involved in regulation of these processes are discussed as well as disorders associated with their malfunction, and lamellar bodies-independent secretion is also considered.
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