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

Riedemann, Niels C.; Guo, Ruocheng; Sarma, Vidya; Laudes, Ines J.; Huber‐Lang, Markus; Warner, Roscoe L.; Albrecht, Eric A.; Speyer, Cecilia L.; Ward, Peter A.

doi:10.4049/jimmunol.168.4.1919

Cited by 89 publications

(63 citation statements)

References 38 publications

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“…The answer to this question awaits the finding of receptors to C5a at the apical face of the mammary epithelial cells and the determination of their functional ability. At other epithelial surfaces such as the lungs of rats, the outcome of the exposure of alveolar epithelial cells to C5a is the release of proinflammatory cytokines and the enhanced expression of the C5a receptor, leading to an enhanced phlogistic response [97]. There is some indirect evidence that mammary epithelial cells react to C5a [76,105].…”

Section: The Biological Significance Of the Complement In Milk And Armentioning

confidence: 99%

The complement in milk and defense of the bovine mammary gland against infections

Rainard

2003

Vet. Res.

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-The mammary gland of dairy cows, which is prone to infection by various bacteria, mobilizes local and systemic immune defenses to cope with pathogens. The complement system plays an important part in the innate immunity against microorganisms through its bactericidal, opsonic, and phlogistic functions. The amount of the complement in the milk of healthy glands of dairy cows is low. Moreover, the classical pathway of activation is not functional because of a shortage in C1q. By contrast, the alternative pathway is active, deposits C3b and C3bi on bacteria, and generates amounts of C5a which are highly variable among cows. A slight inhibition of the bactericidal/hemolytic activities, of the deposition of C1q on bacteria, and of the phlogistic activity of C5a makes milk a rather anti-inflammatory fluid. The inhibitory activity does not involve C3b/ C3bi deposition on bacteria, nor the generation of C5a by the alternative pathway. When inflammation develops, the blood-derived complement components overcome the inhibitions and complement-dependent bactericidal, opsonic and phlogistic activities may be high in milk. Further research is necessary to evaluate the contribution of C5a to the recruitment of leukocytes in the mammary gland, and to specify the links between the complement system and the response of resident cells (leukocytes and mammary epithelial cells) to infection stimulus. This will help to define the contribution of the complement system to resistance against mastitis, and could help to differentiate animals more or less resistant to this frequent and costly disease.

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Section: The Biological Significance Of the Complement In Milk And Armentioning

confidence: 99%

The complement in milk and defense of the bovine mammary gland against infections

Rainard

2003

Vet. Res.

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“…This injury has been attributed to biological effects of C5a and MAC. C5aR has been localized by immunohistology on bronchial and alveolar epithelial cells as well as vascular smooth muscle and endothelial cells of human lung tissue (26,28,57,58). The potential for tissue activation through the C5aR has been verified for endothelial cells in culture.…”

Section: Figurementioning

confidence: 99%

“…C5a is a powerful chemotactic and activating factor for neutrophils, macrophages, eosinophils, and mast cells. In addition, C5a induces the release of chemokines and cytokines from pulmonary macrophages and epithelial cells (26,27). C5a has also been shown to activate endothelial cells of pulmonary vessels, resulting in surface expression of P-selectin (24,28).…”

mentioning

confidence: 99%

Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection

Nakashima

Qian

Rahimi

et al. 2002

The Journal of Immunology

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The lung is known to be particularly susceptible to complement-mediated injury. Both C5a and the membrane attack complex (MAC), which is formed by the terminal components of complement (C5b-C9), can cause acute pulmonary distress in nontransplanted lungs. We used C6-deficient rats to investigate whether MAC causes injury to lung allografts. PVG.R8 lungs were transplanted orthotopically to MHC class I-incompatible PVG.1U recipients. Allografts from C6-sufficient (C6+) donors to C6+ recipients were rejected with an intense vascular infiltration and diffuse alveolar hemorrhage 7 days after transplantation (n = 5). Ab and complement (C3d) deposition was accompanied by extensive vascular endothelial injury and intravascular release of von Willebrand factor. In contrast, lung allografts from C6-deficient (C6−) donors to C6− recipients survived 13–17 days (n = 5). In the absence of C6, perivascular mononuclear infiltrates of ED1+ macrophages and CD8+ T lymphocytes were present 7 days after transplantation, but vascular endothelial cells were quiescent, with minimal von Willebrand factor release and no evidence of alveolar hemorrhage or edema. Lung allografts were performed from C6− donors to C6+ recipients (n = 5) and from C6+ donors to C6− recipients (n = 5) to separate the effects of systemic and local C6 production. Lungs transplanted from C6+ donors to C6− recipients had increased alveolar macrophages and capillary injury. C6 production by lung allografts was demonstrated at the mRNA and protein levels. These results demonstrate that MAC causes vascular injury in lung allografts and that the location of injury is dependent on the source of C6.

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“…17 Recently, C5a has been shown to be involved in modulation of cytokine expression from various cell types. 18,19 C5a exerts its effects through the high-affinity receptors, mainly CD88 (C5aR). C5aR expression was not only described on myeloid cells, including neutrophils and macrophages, but also found on a variety of nonmyeloid cells in many organs, [20][21][22] which suggests the implication of C5a/C5aR signaling in the pathogenesis of organ-specific inflammation.…”

mentioning

confidence: 99%

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Chen¹,

Yang

Gao

et al. 2011

Laboratory Investigation

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Complement represents a chief component of innate immunity in host defense. However, excessive complement activation has been involved in the pathogenesis of inflammatory diseases. In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (À2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD. The inflammatory bowel diseases (IBDs) encompassing Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of gastrointestinal tract, characterized by dysfunction of mucosal T cells, abnormal cytokine production, cellular inflammation, and ultimately damage to the intestinal lining. 1 Although the etiology of IBD remains unknown, there is circumstantial evidence to link IBD to the mucosal immune system's failure to attenuate immunity to endogenous antigen. 1 In recent years, several animal IBD models have been developed. 2,3 Although the relationship of many of these models to human disease is imperfect, the hapten-induced model of colonic inflammation in which 2,4,6-trinitrobenzene sulfonic acid (TNBS) is delivered intrarectally to BALB/c mice displays human CD-like features, notably predominantly IL-12-driving Th1 activity of the mucosal CD4 þ T-cell population and transmural mononuclear inflammation. 3 More recently, a pathogenic role of IL-23, the cytokine sharing p40 subunits with IL-12, has been evidenced in the development of CD. 4 Deficiency of IL-23-specific subunits (p19) leads to failure of colitis induction in a T-cell transfer model. This effect is attributed to suppression of IL-17 production and Th17 differentiation in the colons. 5 The factors that initiate intestinal pathology of CD and elicit Th1/Th17 immune reaction, however, are still

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

Cited by 89 publications

References 38 publications

The complement in milk and defense of the bovine mammary gland against infections

The complement in milk and defense of the bovine mammary gland against infections

Membrane Attack Complex Contributes to Destruction of Vascular Integrity in Acute Lung Allograft Rejection

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

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