Expression of C5a receptors (CD 88) on human bronchial epithelial cells (HBEC): C5a-mediated release of IL-8 upon HBEC exposure to cigarette smoke

Floreani, Anthony A.; Heires, Art J.; Clark-Pierce, Laurel; Li, Renhao; Miller-Lindholm, Amanda K.; Rennard, S. I.; Morgan, Eric Lease; Sanderson, Sam D.

doi:10.1007/0-306-46862-x_237

Cited by 29 publications

(41 citation statements)

References 2 publications

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“…Increased mRNA for C5aR after exposure of hepatocytes to IL-6 has been recently described (25). In human bronchial epithelial cells, up-regulation of C5aR occurs following exposure to cigarette smoke linked with enhanced production of IL-8 in response to C5a (30). Recently, it has been reported that induction of intracerebral C5aR in mice following closed head injury is due, at least in part, to TNF-␣ production (31), which seems to support our results in RAEC.…”

Section: Discussionmentioning

confidence: 96%

Expression and Function of the C5a Receptor in Rat Alveolar Epithelial Cells

Riedemann

Guo

Sarma

et al. 2002

The Journal of Immunology

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Although alveolar epithelial cells (AEC) form an important barrier for host defenses in the lung, there is limited information about ways in which AEC can directly participate in the lung inflammatory response. In the current studies, primary cultures of rat AEC (RAEC) have been shown to specifically bind recombinant rat C5a at high affinity and in a saturable manner. This binding was enhanced in a time-dependent manner by pre-exposure of RAEC to LPS, IL-6, or TNF-α, the increased binding of C5a being associated with increased levels of mRNA for the C5a receptor (C5aR). Exposure of RAEC to C5a also caused increased expression of mRNA for C5aR. As compared with exposure of RAEC to LPS or to C5a alone, exposure to the combination caused enhanced production of TNF-α, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant-1, as well as increased intracellular levels of IL-1β. These data indicate that RAEC, when activated, have enhanced binding of C5a in association with increased mRNA for C5aR. The functional outcome is enhanced release of proinflammatory mediators. These data underscore the phlogistic potential of RAEC and the ability of C5a to enhance the phlogistic responses of RAEC.

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Section: Discussionmentioning

confidence: 96%

Expression and Function of the C5a Receptor in Rat Alveolar Epithelial Cells

Riedemann

Guo

Sarma

et al. 2002

The Journal of Immunology

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“…C5aR, initially thought to be present mainly on leukocytes and most abundantly in cells of the myeloid lineage (29), appears to be expressed in many nonhematopoietic cell types including the epithelia of kidney and lung (1,14,16,26,41,54), suggesting new physiological roles. However, studies on normal human intestine using mAbs P12/1 and D12/1 by Fayyazi and colleagues (15,58) failed to detect IEC expression.…”

Section: Discussionmentioning

confidence: 99%

Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway

Cao

McIsaac

Stadnyk

2012

American Journal of Physiology-Cell Physiology

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Intestinal epithelial cells (IECs) exhibit numerous adaptations to maintain barrier function as well as play sentinel roles by expressing receptors for microbial products and antimicrobial peptides. The complement system is another important innate sensing and defense mechanism of the host against bacteria and increasing evidence shows that complement plays a role in colitis. The split component C5a is a potent proinflammatory molecule, and the C5a receptor (C5aR) CD88 has been reported on multiple cell types. Here, we examined the question of whether human colonic cell lines can detect activated complement via C5aR and what signaling pathway is critical in the subsequent responses. T84, HT29, and Caco2 cell lines all possessed mRNA and protein for C5aR and the decoy receptor C5L2. Polarized cells expressed the proteins on the apical cell membrane. C5a binding to the C5aR on human IECs activates the ERK pathway, which proved critical for a subsequent upregulation of IL-8 mRNA, increased permeability of monolayers, and enhanced proliferation of the cells. The fact that human IECs are capable of detecting complement activation in the lumen via this anaphylatoxin receptor highlights the potential for IECs to detect pathogens indirectly through complement activation and be primed to amplify the host response through heightened inflammatory mediator expression to further recruit immune cells.

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“…Only recently as new blocking agents have become available (antibodies to C5aR or antagonists to C5aR), more attention has been paid to the potential role of C5aR in various organs (14,16,(23)(24)(25). C5a is responsible for a broad variety of effects in different tissues, as described above.…”

Section: Discussionmentioning

confidence: 99%